Genome-wide analysis of histone modifiers in tomato: gaining an insight into their developmental roles
- Riccardo Aiese Cigliano†1,
- Walter Sanseverino†2,
- Gaetana Cremona1,
- Maria R Ercolano2,
- Clara Conicella1 and
- Federica M Consiglio1Email author
© Cigliano et al.; licensee BioMed Central Ltd. 2013
Received: 16 July 2012
Accepted: 22 January 2013
Published: 28 January 2013
Histone post-translational modifications (HPTMs) including acetylation and methylation have been recognized as playing a crucial role in epigenetic regulation of plant growth and development. Although Solanum lycopersicum is a dicot model plant as well as an important crop, systematic analysis and expression profiling of histone modifier genes (HMs) in tomato are sketchy.
Based on recently released tomato whole-genome sequences, we identified in silico 32 histone acetyltransferases (HATs), 15 histone deacetylases (HDACs), 52 histone methytransferases (HMTs) and 26 histone demethylases (HDMs), and compared them with those detected in Arabidopsis (Arabidopsis thaliana), maize (Zea mays) and rice (Oryza sativa) orthologs. Comprehensive analysis of the protein domain architecture and phylogeny revealed the presence of non-canonical motifs and new domain combinations, thereby suggesting for HATs the existence of a new family in plants. Due to species-specific diversification during evolutionary history tomato has fewer HMs than Arabidopsis. The transcription profiles of HMs within tomato organs revealed a broad functional role for some HMs and a more specific activity for others, suggesting key HM regulators in tomato development. Finally, we explored S. pennellii introgression lines (ILs) and integrated the map position of HMs, their expression profiles and the phenotype of ILs. We thereby proved that the strategy was useful to identify HM candidates involved in carotenoid biosynthesis in tomato fruits.
In this study, we reveal the structure, phylogeny and spatial expression of members belonging to the classical families of HMs in tomato. We provide a framework for gene discovery and functional investigation of HMs in other Solanaceae species.
Chromatin is characterized by a dynamic multi-level organization passing through the nucleosomal basic unit, the 30-nm fiber, and higher-order folding up to the chromosome . Nucleosome remodeling, histone post-translational modifications (HPTMs), DNA methylation, and other factors contribute to define different chromatin states which drive transcription and other chromatin-based nuclear processes [2–4]. In particular, HPTMs correlate largely with transcriptional regulation, but they are also involved in DNA replication, histone deposition, and DNA repair and recombination. HPTMs occurring in core histone tails include a variety of covalent modifications including acetylation, methylation, phosphorylation, and ubiquitination . Histone acetylation is a reversible process carried out by two classes of enzymes known as histone acetylases (HATs) and histone deacetylases (HDACs) acting on the ε-amino group of lysine residues in histones. The acetylation targets in the H3 tail are lysine (K) residues 9, 14, 18 and 23, and in H4 lysine (K) residues 5, 8, 12, 16 and 20 .
HATs and HDACs are classified into different families that are generally conserved in eukaryotes, including yeast, animals, and plants. Plant HATs are currently categorized into four groups on the basis of homology with other eukaryotic HATs and domain composition: (i) HAG with Acetyltransf_1 domain (PF00583) (AT1) include GCN5-, ELP3-, HAT1-like acetyltransferases; (ii) HAM with a MYST (MOZ-YBF2/SAS3-SAS2-TIP60) domain; (iii) HAC with similarity to p300/CREB-binding protein; (iv) HAF related to the TATA binding protein-associated factor 1 . Specific HATs acetylate H4K5 (HAM members), H4K12 and H3K14 (HAG members). Other acetylation marks, including H3K9, are likely to result from the activities of HAC members with broad specificity . Plant HDACs are grouped into three families: RDP3/HDA1, hereinafter named HDAs, SIR2 and HD2. Two of these families are homologous to HDACs found in yeast and animals while the HD2 family appears to be unique to plants and unrelated to the other families . Of all HPTMs, acetylation has the most potential to unfold chromatin since it neutralizes the basic charge of the lysine . In the histones, HDACs remove acetyl groups added by HATs by resetting the chromatin structure for the transcription. Furthermore, HDACs and HATs can function in protein complexes as transcriptional co-repressors and co-activators [8–10] or associated with chromatin remodelers as modulators of the accessibility of DNA to different machineries.
In Arabidopsis, HDACs and HATs are emerging as crucial players in growth and development processes, including meiotic recombination, embryogenesis, flowering, and senescence as well as in responses to environmental cues [11, 12]. While histone acetylation is dynamically regulated by HATs and HDACs, histone methylation is balanced by the activities of histone methylases (HMTs) and histone demethylases (HDMs) . Plant histone methyltransferases are assigned to different protein groups based on sequence similarity with SET domains (SDG) found in Drosophila SU(VAR)3-9, Enhancer of Zeste E(z), Tritorax (TRX), and absent, small, or homeotic discs (ASH1). These proteins function in covalent addition of one (me1), two (me2) or three (me3) methyl groups to lysine residues in histone tails H3K4, H3K9, H3K27, H3K36, and H4K20. Arabidopsis SU(VAR)3-9 members have H3K9 methyltransferase activity and play a key function predominantly in heterochromatin formation and gene silencing [14–18]. Enhancer of Zeste E(z) proteins catalyze H3K27 trimethylation and are involved in the repressive control of gene expression . TRX proteins mediate H3K4 methylation and are required for transcriptional gene activation as well as ASH1 proteins that have a dual methyltransferase function for both H3K4 and H3K36 . Histone methylation occurs also at the arginine residues and is catalyzed by protein arginine methyltransferase (PRMTs) . Arabidopsis histone methyltransferases and their importance in relation to plant development have recently been reviewed . Histone methylation has long been regarded as an irreversible mark until the discoveries in mammals of two families of HDMs, KDM1 (histone lysine demethylase 1) also known as lysine-specific demethylase 1 (LSD1) and the JmjC domain (Jumonji C) containing proteins . Arabidopsis homologs of human LSD1 act to reduce the level of H3K4 methylation. They were discovered at the level of floral repressor FLOWERING LOCUS C (FLC), a key component of a regulatory network that controls the timing of the start of flowering . The JmjC proteins are able to remove the methyl group on H3K4, H3K9, H3K27 and H3K36 [25, 26]. Unlike KDM1, these proteins could reverse all the states (me1, me2, me3) of lysine methylation [21, 27–29]. Furthermore, a member of the JmjC proteins has been shown to demethylate arginine H3R2 and H4R3 in animal cells . However, arginine demethylase activity remains to be determined in plants. Recent studies have revealed a role for Arabidopsis JmjC proteins in several aspects of plant development such as floral transition [26, 28, 29], gametophyte function , and circadian rhythm [32, 33].
In spite of the crucial role emerging for epigenetic modifications in plant growth and development, little is known regarding HMs in the important crop Solanum lycopersicum. Using the complete sequence of tomato genome as well as transcriptomes at different stages/organs  we investigated HM genes through a bioinformatic approach. In this study we give a comprehensive overview of the structure, phylogeny and spatial expression of members belonging to the classical families of HMs in tomato. Furthermore, we shed light on the position of HMs on the tomato genome. We combined this information and HM expression profiles with the phenotype of tomato introgression lines (ILs) in order to identify candidate genes involved in epigenetically regulated processes.
Results and discussion
In this study, 124 histone modifiers (HMs) were identified in tomato. We systematically classified 32 proteins belonging to HATs, 14 to HDACs, 52 to HMTs, and 26 to HDMs.
In order to infer the phylogenic history of tomato HAGs, we compared them with Arabidopsis, maize and rice orthologs. HAGs are distributed in six main clades with high bootstrap values (Figure 1), three of which include monocots and dicots while the other three include only dicots. Each clade contains one tomato HAG family, except HPA2 whose members are split into two clades. Interestingly, a subclade of HPA2 members includes eight genes (SlHAG11, SlHAG19-22, SlHAG24-26) that are all closely localized on chromosome 8 in a cluster of about 82 Kb. This finding suggests that the ancestral locus experienced a series of tandem duplication events.
The existence of so many HAG members in the tomato proteome compared with Arabidopsis as well as monocots led us to investigate HAGs in Arabidopsis in greater depth. BLAST search using the AT1 domain as a query returned 33 proteins in Arabidopsis, thereby giving a number close to tomato. Based on the domain composition, in Arabidopsis we identified At2g22910 and At4g37670 which in addition to AT1 have the AAK domain (PF00696). Similarly to tomato, it is likely that these two proteins are not histone acetylases. Phylogenetic analysis of tomato and Arabidopsis HAGs indicates that the different subgroups evolved differently in these species (see Additional file 1). For example, gene duplication events giving rise to the subgroup including SlHAG19 to SlHAG26 likely occurred only in tomato while the orthogroup that comprises SlHAG6 appears to have experienced an expansion only in Arabidopsis.
As mentioned above, SlHAG4 is a peculiar HAG, having both the typical HAT1_N domain and an MOZ_SAS domain. In order to understand the origin of this combination of domains, we performed extensive research through Interpro (http://www.ebi.ac.uk/interpro) into the genomes of fully sequenced organisms (http://www.ncbi.nlm.nih.gov/sites/genome) and particularly in plants (http://www.phytozome.org). Intriguingly, a domain structure similar to that of SlHAG4 was found mostly in plants and additionally in the brown alga Ectocarpus siliculosus (Chromoalveolata) and in Trichoplax adhaerens (Animalia). The existence of SlHAG4-like proteins in different organisms suggests that histone acetylases with both HAT1_N and MOZ_SAS domains can be categorized as members of a new family which we name GNAT/MYST-Like (GML).
Additional file 2 shows the proteins with the highest similarity to SlHAG4. Out of 32 species belonging to Plantae, 12 evidenced proteins with both HAT1_N and MOZ_SAS domains. Interestingly, these species are not randomly distributed among the different orders. Indeed, GML proteins seem to be lacking in Brassicales, Poales, Ranunculales and Volvocales, although the scant sequence data suggest caution regarding this finding. The distribution of GML proteins in Planta, Animalia and in Chromoalveolata suggests that the combined domains AT1 and MOZ_SAS occurred early on in evolutionary history. However, most of the organisms show HAT1_N and MOZ_SAS domains in two functional distinct families, GNAT and MYST histone acetylases, respectively. Due to lack of information about the biological function of GML proteins, we can only speculate that the separation of the two domains could confer an advantage for nuanced control of the histone acetylation level in the genome.
The tomato proteome has one MYST acetyltransferase, namely SlHAM1, that is a 477-aa long protein characterized by N-terminal Chromo (PF00385), C2H2 (PF00096), and C-terminal MOZ_SAS (PF01853) domains, that are typical of class I HAMs . Previous studies have shown that other plant HAMs belong only to the class I . Phylogenetic analysis (see Additional file 3) shows that HAMs are distributed in two clades, one of which includes tomato as well as Arabidopsis proteins. The other clade contains two proteins from monocots, maize and rice. This separation indicates that a single ancestral HAM gene gave rise to HAMs in monocots and dicots, being a specific event of duplication at the origin of the expansion of this family in Arabidopsis and maize. The expression pattern of SlHAM1 shows that it is expressed in all the examined organs with the highest expression in flowers and in 3 cm fruit (Figure 2). Latrasse and colleagues  found that AtHAM1 and AtHAM2 are strongly expressed in flowers and act redundantly in male and female gametophyte development. This evidence suggests that SlHAM1, in addition to its putative role in seed and/or fruit development, could play a role in gametogenesis like the Arabidopsis ortholog.
In order to gain insight into the possible role of tomato HACs, we examined their expression profiles in different tomato organs (Figure 2). SlHAC4 shows the strongest expression in fruit at different developmental stages. It is interesting that the peak of SlHAC4 expression occurs in mature green berries and is followed by a strong reduction in fruit at breaker stage, thereby suggesting a role in the transition between these two fruit developmental stages. SlHAC1 and SlHAC2, forming a distinct clade, are the most widely expressed tomato HACs, with the latter showing lower expression values. Similarity between SlHAC1 and SlHAC2 in terms of sequence and expression profile in reproductive organs suggests a functional redundancy that is analogously reported for Arabidopsis homologs AtHAC1/AtHAC5 and AtHAC1/AtHAC12. The presence of SlHAC1 and SlHAC2 in the same clade of Arabidopsis AtHAC1, AtHAC5 and AtHAC12 further supports a role of these proteins in tomato reproduction. Indeed, knockdown of AtHAC1 induced reduced fertility and late flowering  and analysis of hac1/hac5 and hac1/hac12 double mutants highlighted their role in flowering time in Arabidopsis . SlHAC3 is likely a pseudogene since it does not appear to be expressed in the tissues under analysis.
Tomato proteome has one TAFII250 protein (SlHAF1) (Figure 3B) that shows the same domain composition of Arabidopsis, rice and maize HAFs . Phylogenetic comparison with these species evidenced that SlHAF1 forms a distinct clade with AtHAF1 and AtHAF2 separated from OsHAF701 and ZmHAF101 (Figure 3B). Interestingly, SlHAF1, albeit expressed in all the organs considered, has the strongest expression in roots and in fruit, particularly in berries ten days after breaking, thereby suggesting an important role in fruit maturation (Figure 2).
In order to understand the candidate function of tomato HDAs, we looked at their expression profiles (see Additional file 4). Given the wide range of expression values, we categorized the tomato HDAs in three groups having low (see Additional file 4A), middle (see Additional file 4B) and high expression (see Additional file 4C). SlHDA2 expressed mostly in root and bud is the lowest expressed gene among the tomato HDAs. Its expression profile suggests a role in highly dividing tissues such as root and flower meristems. The middle-expressed HDA members show very different expression profiles. Among them, SlHDA9 could exert a possible role in root development as supported by its strong expression in this organ and by its similarity to AtHDA5 and AtHDA18 . A complementary role of SlHDA5, SlHDA6 and SlHDA7 in fruit development from 1 cm to B10 stage is suggested by their peaks of expression in these stages. Finally, the highly expressed SlHDA1 and SlHDA3 show the strongest expression at B10 and B fruit stages, respectively, thereby supporting a possible role in tomato fruit ripening. SlHDA1 and SlHDA3 have respectively a sequence similarity with AtHDA6 and AtHDA19 that in Arabidopsis have been linked to flowering, embryo development and other biological processes [11, 46, 47].
In the tomato proteome, we identified two histone deacetylases belonging to the SIR2 family, namely SlSRT1 and SlSRT2 (see Additional file 5). They are characterized by an SIR2 domain (PF02146) and correspond to LeSRT1105 and LeSRT1104, previously described by Pandey and colleagues . The expression profiles of tomato SRT genes evidence expression peaks of SlSRT1 in bud and in 1 cm-sized fruit while SlSRT2 was expressed in flower and in fruit at B10 (see Additional file 4). These findings suggest that SlSRT1 could play a role in the early stages of fruit development as well as in early gamete development whereas SlSRT2 is involved later in both fruit ripening and in gametogenesis. The expression profile of SlSRT2 also supports a role in FLC regulation as suggested for Arabidopsis counterparts by Bond and colleagues .
According to the results of Pandey and colleagues  who described three HDTs in tomato proteome (HDT1101, HDT1102, HDT1103) we found SlHDT1, SlHDT2 and SlHDT3 corresponding to HDT1102, HDT1103 and HDT1101, respectively (see Additional file 6). SlHDT2 shows a C-terminal zinc finger domain in addition to the predicted HD2 domain (EFWG motif at the N-terminus). The evolutionary history of plant HDTs, including those of tomato, was well illustrated by Pandey and colleagues . As shown in Additional file 4, the preferential expression of tomato HDTs occurs at early stages of fruit development. In particular, SlHDT1 is highly expressed in 1 cm fruit, SlHDT2 in both 1 cm- and 3 cm-sized fruits, SlHDT3 in 3 cm fruit and in mature green berries. Overall, these expression profiles suggest a role of tomato HDTs in fruit development. Interestingly, tomato HDTs seem to be all closely related to AtHDT3 (see Additional file 6) that was shown to be involved in ABA response and seed germination .
As regards class II SDGs, some genes with very specific peaks of expression may be noted. Indeed, SlSDG35 is strongly expressed in leaves, SlSDG34 in fruit at the 3 cm stage, SlSDG17 in flowers, and SlSDG19 in buds. These expression profiles suggest a possible wide subfunctionalization of class II SDGs in tomato with a low degree of redundancy. A role in fruit development could be played by SlSDG33 with an expression profile similar to AtSDG8 which regulates gene expression in the carotenoid pathway . SlSDG16 is mostly expressed in buds and in the early stages of fruit development. Interestingly, this gene could share some functions with its Arabidopsis counterpart, AtSDG4. Indeed, the latter mainly expressed in pollen is involved in pollen tube growth and reproduction in Arabidopsis . SlSDG18 and SlSDG36 were noticed to behave like pseudogenes, not being expressed in any of the organs analyzed.
Among the class III SDGs, SlSDG29, SlSDG44 and SlSDG26 could play redundant roles in root development, as could SlSDG20 and SlSDG29 in fruit maturation. The latter is closely related to AtSDG2 which was shown to affect vegetative growth and reproduction in Arabidopsis by regulating the expression of hundreds of genes [54, 55]. Moreover, the expression profile of AtSDG2 is similar to that of SlSDG29 in comparable organs, thereby supporting the idea of similar functions. SlSDG44 is related to AtSDG27 that was shown to regulate the expression of a xyloglucanase  which belongs to a class of enzymes involved in tomato fruit ripening . In a similar fashion, SlSDG44 could act in fruit ripening since it is highly expressed in fruits, particularly at the MG stage. On the contrary, some degree of functional divergence seems to have occurred between SlSDG20 and its homolog AtSDG25 involved in flowering time in Arabidopsis . Indeed, the latter is more expressed in flowers while SlSDG20 is very poorly expressed in this organ.
The two members of tomato Class IV SDGs have different expression profiles: while SlSDG27 is strongly expressed in roots and fruit at the 1 cm stage, SlSDG28 is mostly expressed in buds and in fruit at the B10 stage. These differences suggest that the two genes evolved different functions, with SlSDG28 being mainly involved in reproduction.
Tomato SDGs of class V may show a high degree of redundancy in some functions. Indeed, SlSDG3, SlSDG9, SlSDG6 and SlSDG5 have their highest expression in fruit at 1 cm and 2 cm, SlSDG2, SlSDG14, SlSDG13, SlSDG4 and SlSDG10 have their peak expression in fruit at the 3 cm stage, while SlSDG1 and SlSDG7 are particularly expressed in fruit at MG up to B10 stages. Therefore, these expression profiles suggest that they might play roles in fruit and/or seed at sequential stages of development. Moreover, SlSDG9 is highly expressed in buds as well as SlSDG12 and SlSDG8, suggesting that they could have a function in meiosis or in flower development.
As with the above-reported SDGs, also the members of classes VI and VII may have a possible redundant function. For example, SlSDG30, SlSDG41 and SlSDG42 are highly expressed in 1 cm fruit while SlSDG32, SlSDG39 and SlSDG38 in 3 cm fruit, thereby suggesting sequential functions in embryo/fruit development. A more specific expression profile is shown by SlSDG40 which evidenced peak expression in the bud, indicating a role in gamete and/or flower development. However, the putative involvement of these genes in development has not been investigated in any plant species.
We identified nine PRMTs in tomato (SlPRMT1 to SlPRMT9). SlPRMT8 was already described by Krause and colleagues  and was named PAM1.1. Specific patterns in the catalytic AdoMet_Mtase domain (CD02440)  allowed us to categorize SlPRMT1, 2, 3, 5, 7, and 9 as class I PRMTs while SlPRMT4 and SlPRMT6 belong to class II (see Additional file 7). For class I some duplication events were highlighted in dicot species.
The expression profiles of tomato PRMTs (see Additional file 8) suggest functional redundancy among these genes since some organs are characterized by two or more PRMTs with high expression levels. This is the case of roots where SlPRMT9, SlPRMT7 and SlPRMT3 have their relative strongest expression. SlPRMT8, SlPRMT2, and SlPRMT5 were expressed in fruit at the 1 cm stage while SlPRMT4 and SlPRMT1 at the B10 stage. To investigate the biological function of SlPRMTs, we considered the role of orthogroups in Arabidopsis. SlPRMT5 and SlPRMT8 belong to the same clade as AtPRMT11 and AtPRMT12. The latter were suggested to be in the same histone methylation complex on the basis of their physical interaction  and spatial expression profiles. By contrast, SlPRMT5 and SlPRMT8 have quite different expression profiles and, when similar organs are compared between the two species, only the first has a profile resembling that of Arabidopsis counterparts. On this basis, we hypothesize that SlPRMT5 and SlPRMT8 evolved independent functions, with SlPRMT5 perhaps retaining the biological role of AtPRMT11 and AtPRMT12. If this is true, SlPRMT5 should be involved in flowering time, flower morphology and fertility as well as in leaf development . SlPRMT7 is the closest homolog to AtPRMT10 which was shown to be a component in the autonomous pathway which controls the floral transition in an FLC-dependent manner . Since the expression profiles of these two genes are comparable, SlPRMT7 might also have a functional role in flowering time. SlPRMT3 and SlPRMT9 grouped with AtPRMT13 and AtPRMT14 that were shown to redundantly control the floral transition . Accordingly to their functional redundancy, AtPRMT13 and AtPRMT14 have very similar expression profiles. On the other hand, SlPRMT3 and SlPRMT9 differ greatly in expression profile, also vis-à-vis their Arabidopsis counterparts, when similar organs are compared . SlPRMT3 and SlPRMT9 could play different roles in tomato development and might not be involved in flowering time. SlPRMT6 is the closest homolog to AtPRMT5, which was shown to be involved in vegetative growth and flowering time [64, 65]. The different expression profiles of AtPRMT5 and SlPRMT6 suggest that the latter evolved a different role possibly in fruit maturation as evidenced by its expression peak in fruit at the MG stage.
In tomato, we identified 34 proteins showing similarity to HDMA histone demethylases. All are characterized by the C-terminal Amino_Oxidase domain (AOD) (PF01593) but only six (SlHDMA1 to SlHDMA6) also have the N-terminal SWIRM (PF04433) domain that is conserved in all HDMAs. As shown in Additional file 9, HDMAs proteins are distributed in two main clades, comprising one (SlHDMA6) and five tomato members (SlHDAM1-5). Phylogenetic analysis suggests that four ancestors gave rise to the present number of HDMAs in tomato, and accordingly at least two events of gene duplication increased the number of HDMAs from four to six. In particular, SlHDMA1, 2 and SlHDMA4, 5 could have been arisen from a tandem duplication event as suggested by their close position on chromosome seven (not shown).
The Additional file 10 shows the expression profile of tomato HDMAs, divided into three groups with low (A), mild (B) and high (C) expression. SlHDMA2 is barely detectable in buds and in fruit from 2 cm stage to B, while SlHDMA5 is mostly expressed in buds and flowers, suggesting a major role of the former gene in fruit development and the latter gene in gamete and/or flower development. SlHDMA4 and SlHDMA6 are detectable in all organs, pointing out a possible role for these genes throughout development including reproductive stages. SlHDMA1 is quite uniformly expressed in all plant organs and SlHDMA3 has a clear preferential expression in fruit from 2 cm stage to B10. Collectively, these profiles indicate that tomato HDMAs could play redundant roles in different aspects of fruit development and SlHDMA3 could be the major histone demethylase in tomato. Moreover, SlHDMA3 could play a role both in flowering time and root elongation, as suggested by its expression profile and its sequence similarity to AtHDMA3 [66, 67].
The tomato proteome reveals 20 proteins belonging to the JMJ family of HDMs. On the basis of their domain composition we classified them in five classes that take their names from their human counterparts: JMJC-only, KDM4, JMJD6, KDM5 and KDM3 . The tomato JmjC-only class includes three proteins (SlJMJ10-11, and SlJMJ18), the KDM4 class five proteins (SlJMJ1-5), and KDM5 class four proteins (SlJMJ6-8, and SlJMJ16). The classes JMJ6 (SlJMJ9 and SlJMJ12) and KDM3 (SlJMJ13-15, SlJMJ17, and SlJMJ19-20) include two and six members, respectively.
The wide expression profile of tomato JMJs (see Additional file 10) in several organs suggests that they could play a global role in plant development. However, some JMJs showed specific expression peaks, thereby suggesting particular roles. This is the case of SlJMJ17 and SlJMJ7 which are preferentially expressed in roots while SlJMJ3, SlJMJ8, SlJMJ4 and SlJMJ20 in buds and/or flowers, suggesting a role in gamete formation or flower development. Interestingly, SlJMJ8 is the closest homolog to AtJMJ14, which is highly expressed in flowers  and acts as a repressor of the photoperiodic pathway . SlJMJ12, SlJMJ16, SlJMJ5 and SlJMJ13 are particularly expressed in fruit at B10, thus suggesting a role in later processes of fruit and/or embryo/seed development.
Association of tomato HMs to S. pennellii introgression lines (ILs): a case study
To identify candidate genes involved in epigenetically regulated processes by means of in silico analysis we looked for ILs where HMs were associated, based on their map position on the tomato genome (see Additional file 12). We failed to recover ILs for SlHAG15, which is not assigned to any chromosome (chr), and for SlJMJ4 (chr4), SlPRMT6 (chr8), SlSDG5 (chr2), SlSDG35 (chr12), SlSDG43 (chr1) located terminally on different chromosomes outside the available markers. We then combined the information about the phenotype of ILs with HM expression profiles described in the previous sections.
As a case study, we report the identification of a candidate HM involved in carotenoid biosynthesis in tomato fruits. It should first be noted that the Arabidopsis histone methyltransferase AtSDG8 is required for the expression of the carotenoid isomerase AtCRTISO. The tomato homolog of AtCRTISO was characterized by Isaacson and colleagues  as an essential gene for the production of all trans-lycopene. As reported above, our analysis highlighted that two homologs of AtSDG8 occur in tomato, i.e. SlSDG33 and SlSDG34. It should be pointed out that SlSDG33 is a stronger candidate than SlSDG34 as it is involved in CRTISO-like regulation and hence in the carotenoid composition of the tomato fruit. Indeed, similar to what is observed for tomato CRTISO, SlSDG33 is upregulated during fruit ripening (see Additional file 13) with a peak of expression in fruit at B and B10. Furthermore, it maps on IL4-3-2 that is reported to have a QTL affecting fruit color, which is known to be dependent on carotenoid biosynthesis .
It is well known that a large genome dataset accelerates gene discovery in plants. In this study, we identified in silico 124 HMs in tomato including 32 HATs, 14 HDACs, 52 HMTs, and 26 HDMs. The characterization of HM proteins based on domain annotation was very useful for discovering new family members and new families. Indeed, we revised the canonical family annotation of plant HAGs, reporting the existence in plants of HPA2-like proteins, so far described only in fungi. Moreover, we found that HPA2-like proteins represent the largest group of HAGs both in Arabidopsis and in tomato. Furthermore, we identified a new HAT family, named GLM, revealing that it occurs in 12 plant species. Phylogenetic analysis allowed us to trace the evolutionary history of plant HMs, evidencing their diversification among dicot and monocot species included in this study. By analyzing the expression data of all the HMs identified in this study, we were able to provide an overview of the putative role of these genes in tomato development. In this way we supplied useful inputs to discover genes with broader as well as more specific roles. Our datasets might help to address several biological questions and explore the relationship between genomes and phenotypes. Indeed, we propose to combine genome-wide knowledge of HMs with the phenotype information of tomato ILs to prioritize candidate genes involved in the process of interest.
Data collection and prediction of tomato HMs
The protein sequences of histone modifiers (HMs) from Arabidopsis thaliana, Oryza sativa and Zea mays were retrieved from ChromDB (http://www.chromdb.org) and are listed in Additional file 14. In order to complete the catalogue of Arabidopsis HAGs and of maize JMJs, the TAIR10 (http://www.arabidopsis.org) and Zmays166 (http://www.phytozome.net/) proteome were downloaded and a BLAST  search was then performed using as query the catalytic domain Acetyltransf_1 (PF00583) and different members of Arabidopsis JMJ subfamilies, respectively. The proteins showing only the Acetyltransf_1 and the JMJc catalytic domain (PF02373) were selected. All proteins retrieved were annotated with InterProScan, and for each family of HM a multiple alignment with MUSCLE  was performed. The typical domains of each HM family were extracted from the multiple alignments and used to build specific HMM profiles with HMMER v2.1 . The HMM profiles, after calibration, were used as matrix to search for putative HM proteins in the tomato proteome (FASTA file of all predicted proteins of tomato v2.40).
The homologous proteins to SlHAG4 were found by BLAST search against the proteomes of 29 plant organisms (Phytozome v8.0; http://www.phytozome.net). The Interpro database was queried to identify all the proteins showing both the HAT1_N (PF10394) and the MOZ_SAS (PF01853) domains. The list of SlHAG4 homologous proteins and that found in Interpro is reported in Additional file 15.
HM domain identification
The domain composition of HMs from Solanum lycopersicon, Arabidopsis thaliana, Oryza sativa and Zea mays was inferred with SMART  looking for outlier homologs and PFAM domains.
Molecular phylogenetic analysis
Phylogeny history of HMs was inferred within Phylogeny.fr environment (http://www.phylogeny.fr/version2_cgi/index.cgi; ) Each HM protein group was aligned with MUSCLE . Bayesian phylogeny reconstruction using MrBayes (substitution model = Blosum62; number of generations = 100000; sampling frequency = 100; burnin = 1000) was performed for HAC, HAF, HAM, HDMA, HDT, JMJ and SRT protein families. Maximum Likelihood phylogeny reconstruction was employed for HAG, HDA, PRMT and SDG protein families with PhyML. The bootstrap consensus tree was inferred from 100 replicates . The phylogenetic trees were visualized with FigTree 1.3.1 (http://tree.bio.ed.ac.uk/software/figtree/).
Expression data visualization
The expression data of tomato HMs extracted from dataset of the Tomato Genome Consortium  were visualized with Matrix2PNG (http://www.chibi.ubc.ca/matrix2png/bin/matrix2png.cgi; ). The expression data of JMJs, PRMTs and SDGs were normalized to have mean zero and variance one before producing the heat maps. The genes belonging to each HM family were grouped according to their expression profiles in fruits as calculated with MEV 4.8.1 [79, 80] by using the Gene Distance Matrix tool.
Mapping of tomato HM on introgression lines (ILs)
S. pennellii IL bins (IL-bins)  were visualized on the Sol Genomics Network website (http://solgenomics.net). In order to define the starting and ending point of each IL-bin on the tomato genome, edge molecular marker sequences (MMs) were downloaded. Genome coordinates of MMs were retrieved using BLASTn query against the Solanum lycopersicon 2.30 genome (see Additional file 16). The starting coordinate of each tomato HM was then compared to coordinates of MMs to establish associations (see Additional file 12).
The authors wish to thank Prof JJ Giovannoni and Dr Z Fei for helpful advice in bioinformatics. Valuable technical and graphic support was provided by R Paparo and G Guarino, respectively. This work was funded by the Italian Ministry of Education, University and Scientific Research (project GenoPOMpro, PON02_00395_3082360).
- Fransz P, de Jong H: From nucleosome to chromosome: a dynamic organization of genetic information. Plant J. 2011, 66: 4-17. 10.1111/j.1365-313X.2011.04526.x.View ArticlePubMedGoogle Scholar
- Kouzarides T: Chromatin modifications and their function. Cell. 2007, 128: 693-705. 10.1016/j.cell.2007.02.005.View ArticlePubMedGoogle Scholar
- Weber M, Schübeler D: Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol. 2007, 19: 273-280. 10.1016/j.ceb.2007.04.011.View ArticlePubMedGoogle Scholar
- Sadeh R, Allis CD: Genome-wide “re”-modeling of nucleosome positions. Cell. 2011, 147: 263-266. 10.1016/j.cell.2011.09.042.PubMed CentralView ArticlePubMedGoogle Scholar
- Fuchs J, Demidov D, Houben A, Schubert I: Chromosomal histone modification patterns – from conservation to diversity. Trends Plant Sci. 2006, 11: 199-208. 10.1016/j.tplants.2006.02.008.View ArticlePubMedGoogle Scholar
- Pandey R, Müller A, Napoli CA, Selinger DA, Pikaard CS, Richards EJ, Bender J, Mount DW, Jorgensen RA: Analysis of histone acetyltransferase and histone deacetylase families of Arabidopsis thaliana suggests functional diversification of chromatin modification among multicellular eukaryotes. Nucleic Acids Res. 2002, 30: 5036-5055. 10.1093/nar/gkf660.PubMed CentralView ArticlePubMedGoogle Scholar
- Earley KW, Shook MS, Brower-Toland B, Hicks L, Pikaard CS: In vitro specificities of Arabidopsis co-activator histone acetyltransferases: implications for histone hyperacetylation in gene activation. Plant J. 2007, 52: 615-626. 10.1111/j.1365-313X.2007.03264.x.View ArticlePubMedGoogle Scholar
- Utley RT, Ikeda K, Grant PA, Côté J, Steger DJ, Eberharter A, John S, Workman JL: Transcriptional activators direct histone acetyltransferase complexes to nucleosomes. Nature. 1998, 394: 498-502. 10.1038/28886.View ArticlePubMedGoogle Scholar
- Clayton AL, Hazzalin CA, Mahadevan LC: Enhanced histone acetylation and transcription: a dynamic perspective. Mol Cell. 2006, 23: 289-296. 10.1016/j.molcel.2006.06.017.View ArticlePubMedGoogle Scholar
- Yang XJ, Seto E: HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene. 2007, 26: 5310-5318. 10.1038/sj.onc.1210599.View ArticlePubMedGoogle Scholar
- Hollender C, Liu Z: Histone deacetylase genes in Arabidopsis development. J Integr Plant Biol. 2008, 50: 875-885. 10.1111/j.1744-7909.2008.00704.x.View ArticlePubMedGoogle Scholar
- Tian L, Fong MP, Wang JJ, Wei NE, Jiang H, Doerge RW, Chen ZJ: Reversible histone acetylation and deacetylation mediate genome-wide, promoter-dependent and locus-specific changes in gene expression during plant development. Genetics. 2005, 169: 337-345.PubMed CentralView ArticlePubMedGoogle Scholar
- Klose RJ, Zhang Y: Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol. 2007, 8: 307-318. 10.1038/nrm2143.View ArticlePubMedGoogle Scholar
- Jackson JP, Lindroth AM, Cao X, Jacobsen SE: Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature. 2002, 416: 556-560. 10.1038/nature731.View ArticlePubMedGoogle Scholar
- Jackson JP, Johnson L, Jasencakova Z, Zhang X, PerezBurgos L, Singh PB, Cheng X, Schubert I, Jenuwein T, Jacobsen SE: Dimethylation of histone H3 lysine 9 is a critical mark for DNA methylation and gene silencing in Arabidopsis thaliana. Chromosoma. 2004, 112: 308-315. 10.1007/s00412-004-0275-7.View ArticlePubMedGoogle Scholar
- Naumann K, Fischer A, Hofmann I, Krauss V, Phalke S, Irmler K, Hause G, Aurich AC, Dorn R, Jenuwein T, Reuter G: Pivotal role of AtSUVH2 in heterochromatic histone methylation and gene silencing in Arabidopsis. EMBO J. 2005, 24: 1418-1429. 10.1038/sj.emboj.7600604.PubMed CentralView ArticlePubMedGoogle Scholar
- Fischer A, Hofmann I, Naumann K, Reuter G: Heterochromatin proteins and the control of heterochromatic gene silencing in Arabidopsis. J Plant Physiol. 2006, 163: 358-368. 10.1016/j.jplph.2005.10.015.View ArticlePubMedGoogle Scholar
- Ebbs ML, Bender J: Locus-specific control of DNA methylation by the Arabidopsis SUVH5 histone methyltransferase. Plant Cell. 2006, 18: 1166-1176. 10.1105/tpc.106.041400.PubMed CentralView ArticlePubMedGoogle Scholar
- Hennig L, Derkacheva M: Diversity of Polycomb group complexes in plants: same rules, different players?. Trends Genet. 2009, 25: 414-423. 10.1016/j.tig.2009.07.002.View ArticlePubMedGoogle Scholar
- Berr A, Shafiq S, Shen WH: Histone modifications in transcriptional activation during plant development. Biochim Biophys Acta. 2011, 1809: 567-576. 10.1016/j.bbagrm.2011.07.001.View ArticlePubMedGoogle Scholar
- Liu C, Lu F, Cui X, Cao X: Histone methylation in higher plants. Annu Rev Plant Biol. 2010, 61: 395-420. 10.1146/annurev.arplant.043008.091939.View ArticlePubMedGoogle Scholar
- Thorstensen T, Grini PE, Aalen RB: SET domain proteins in plant development. Biochim Biophys Acta. 2011, 1809: 407-420. 10.1016/j.bbagrm.2011.05.008.View ArticlePubMedGoogle Scholar
- Kooistra SM, Helin K: Molecular mechanisms and potential functions of histone demethylases. Nat Rev Mol Cell Biol. 2012, 13: 297-311. 10.1038/nrg3219.PubMedGoogle Scholar
- Jiang D, Yang W, He Y, Amasino RM: Arabidopsis relatives of the human lysine-specific Demethylase1 repress the expression of FWA and FLOWERING LOCUS C and thus promote the floral transition. Plant Cell. 2007, 19: 2975-2987. 10.1105/tpc.107.052373.PubMed CentralView ArticlePubMedGoogle Scholar
- Chen X, Hu Y, Zhou DX: Epigenetic gene regulation by plant Jumonji group of histone demethylase. Biochim Biophys Acta. 2011, 1809: 421-426. 10.1016/j.bbagrm.2011.03.004.View ArticlePubMedGoogle Scholar
- Lu F, Cui X, Zhang S, Jenuwein T, Cao X: Arabidopsis REF6 is a histone H3 lysine 27 demethylase. Nat Genet. 2011, 43: 715-719. 10.1038/ng.854.View ArticlePubMedGoogle Scholar
- Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y: Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004, 119: 941-953. 10.1016/j.cell.2004.12.012.View ArticlePubMedGoogle Scholar
- Jeong JH, Song HR, Ko JH, Jeong YM, Kwon YE, Seol JH, Amasino RM, Noh B, Noh YS: Repression of FLOWERING LOCUS T chromatin by functionally redundant histone H3 lysine 4 demethylases in Arabidopsis. PLoS One. 2009, 4: e8033-10.1371/journal.pone.0008033.PubMed CentralView ArticlePubMedGoogle Scholar
- Lu F, Cui X, Zhang S, Liu C, Cao X: JMJ14 is an H3K4 demethylase regulating flowering time in Arabidopsis. Cell Res. 2010, 20: 387-390. 10.1038/cr.2010.27.View ArticlePubMedGoogle Scholar
- Chang B, Chen Y, Zhao Y, Bruick RK: JMJD6 is a histone arginine demethylase. Science. 2007, 318: 444-447. 10.1126/science.1145801.View ArticlePubMedGoogle Scholar
- Pagnussat GC, Yu HJ, Ngo QA, Rajani S, Mayalagu S, Johnson CS, Capron A, Xie LF, Ye D, Sundaresan V: Genetic and molecular identification of genes required for female gametophyte development and function in Arabidopsis. Development. 2005, 132: 603-614. 10.1242/dev.01595.View ArticlePubMedGoogle Scholar
- Jones MA, Harmer S: JMJD5 functions in concert with TOC1 in the arabidopsis circadian system. Plant Signal Behav. 2011, 6: 445-448. 10.4161/psb.6.3.14654.PubMed CentralView ArticlePubMedGoogle Scholar
- Lu SX, Tobin EM: Chromatin remodeling and the circadian clock: Jumonji C-domain containing proteins. Plant Signal Behav. 2011, 6: 810-814. 10.4161/psb.6.6.15171.PubMed CentralView ArticlePubMedGoogle Scholar
- Tomato Genome Consortium: The tomato genome sequence provides insights into fleshy fruit evolution. Nature. 2012, 485: 635-641. 10.1038/nature11119.View ArticleGoogle Scholar
- Latrasse D, Benhamed M, Henry Y, Domenichini S, Kim W, Zhou DX, Delarue M: The MYST histone acetyltransferases are essential for gametophyte development in Arabidopsis. BMC Plant Biol. 2008, 8: 12-10.1186/1471-2229-8-12.View ArticleGoogle Scholar
- Kalamaki MS, Alexandrou D, Lazari D, Merkouropoulos G, Fotopoulos V, Pateraki I, Aggelis A, Carrillo-López A, Rubio-Cabetas MJ, Kanellis AK: Over-expression of a tomato N-acetyl-L-glutamate synthase gene (SlNAGS1) in Arabidopsis thaliana results in high ornithine levels and increased tolerance in salt and drought stresses. J Exp Bot. 2009, 60: 1859-1871. 10.1093/jxb/erp072.PubMed CentralView ArticlePubMedGoogle Scholar
- Perrella G, Consiglio MF, Aiese-Cigliano R, Cremona G, Sanchez-Moran E, Barra L, Errico A, Bressan RA, Franklin FCH, Conicella C: Histone hyperacetylation affects meiotic recombination and chromosome segregation in Arabidopsis. Plant J. 2010, 62: 796-806. 10.1111/j.1365-313X.2010.04191.x.View ArticlePubMedGoogle Scholar
- Servet C, Conde E, Silva N, Zhou DX: Histone acetyltransferase AtGCN5/HAG1 is a versatile regulator of developmental and inducible gene expression in Arabidopsis. Mol Plant. 2010, 3: 670-677. 10.1093/mp/ssq018.View ArticlePubMedGoogle Scholar
- Nelissen H, Fleury D, Bruno L, Robles P, De Veylder L, Traas J, Micol JL, Van Montagu M, Inzé D, Van Lijsebettens M: The elongata mutants identify a functional Elongator complex in plants with a role in cell proliferation during organ growth. Proc Natl Acad Sci USA. 2005, 102: 7754-7759. 10.1073/pnas.0502600102.PubMed CentralView ArticlePubMedGoogle Scholar
- Nelissen H, De Groeve S, Fleury D, Neyt P, Bruno L, Bitonti MB, Vandenbussche F, Van der Straeten D, Yamaguchi T, Tsukaya H, Witters E, De Jaeger G, Houben A, Van Lijsebettens M: Plant Elongator regulates auxin-related genes during RNA polymerase II transcription elongation. Proc Natl Acad Sci USA. 2010, 107: 1678-1683. 10.1073/pnas.0913559107.PubMed CentralView ArticlePubMedGoogle Scholar
- Kojima S, Iwasaki M, Takahashi H, Imai T, Matsumura Y, Fleury D, Van Lijsebettens M, Machida Y, Machida C: Asymmetric leaves2 and Elongator, a histone acetyltransferase complex, mediate the establishment of polarity in leaves of Arabidopsis thaliana. Plant Cell Physiol. 2011, 52: 1259-1273. 10.1093/pcp/pcr083.View ArticlePubMedGoogle Scholar
- Han SK, Song JD, Noh YS, Noh B: Role of plant CBP/p300-like genes in the regulation of flowering time. Plant J. 2007, 49: 103-114.View ArticlePubMedGoogle Scholar
- Deng W, Liu C, Pei Y, Deng X, Niu L, Cao X: Involvement of the histone acetyltransferase AtHAC1 in the regulation of flowering time via repression of FLOWERING LOCUS C in Arabidopsis. Plant Physiol. 2007, 143: 1660-1668. 10.1104/pp.107.095521.PubMed CentralView ArticlePubMedGoogle Scholar
- Alisung MV, Yu CW, Wu K: Phylogenetic analysis, subcellular localization, and expression patterns of RPD3/HDAI family histone deacetylases in plants. BMC Plant Biol. 2009, 9: 37-10.1186/1471-2229-9-37.View ArticleGoogle Scholar
- Xu CR, Liu C, Wang YL, Li LC, Chen WQ, Xu ZH, Bai SN: Histone acetylation affects expression of cellular patterning genes in the Arabidopsis root epidermis. Proc Natl Acad Sci USA. 2005, 102: 14469-14474. 10.1073/pnas.0503143102.PubMed CentralView ArticlePubMedGoogle Scholar
- Tanaka M, Kikuchi A, Kamada H: The Arabidopsis histone deacetylases HDA6 and HDA19 contribute to the repression of embryonic properties after germination. Plant Physiol. 2008, 146: 149-161.PubMed CentralView ArticlePubMedGoogle Scholar
- Long JA, Ohno C, Smith ZR, Meyerowitz EM: TOPLESS regulates apical embryonic fate in Arabidopsis. Science. 2006, 312: 1520-1523. 10.1126/science.1123841.View ArticlePubMedGoogle Scholar
- Bond DM, Dennis ES, Pogson BJ, Finnegan EJ: Histone acetylation, VERNALIZATION INSENSITIVE 3, FLOWERING LOCUS C, and the vernalization response. Mol Plant. 2009, 2: 724-737. 10.1093/mp/ssp021.View ArticlePubMedGoogle Scholar
- Springer NM, Napoli CA, Selinger DA, Pandey R, Cone KC, Chandler VL, Kaeppler HF, Kaeppler SM: Comparative analysis of SET domain proteins in maize and Arabidopsis reveals multiple duplications preceding the divergence of monocots and dicots. Plant Physiol. 2003, 132: 907-925. 10.1104/pp.102.013722.PubMed CentralView ArticlePubMedGoogle Scholar
- Sadder M, Alsadon A, Al-Thamra M, Zakri A, Al-Doss A: Phylogenetic Analysis of SET Domain in Trithorax SlTX1 of Solanum lycopersicum. Plant Omics. 2011, 4: 95-Google Scholar
- Schmid M, Davison TS, Henz SR, Pape UJ, Demar M, Vingron M, Schölkopf B, Weigel D, Lohmann JU: A gene expression map of Arabidopsis thaliana development. Nature Genet. 2005, 37: 501-506. 10.1038/ng1543.View ArticlePubMedGoogle Scholar
- Cazzonelli CI, Cuttriss AJ, Cossetto SB, Pye W, Crisp P, Whelan J, Finnegan EJ, Turnbull C, Pogson BJ: Regulation of carotenoid composition and shoot branching in Arabidopsis by a chromatin modifying histone methyltransferase, SDG8. Plant Cell. 2009, 21: 39-53. 10.1105/tpc.108.063131.PubMed CentralView ArticlePubMedGoogle Scholar
- Cartagena JA, Matsunaga S, Seki M, Kurihara D, Yokoyama M, Shinozaki K, Fujimoto S, Azumi Y, Uchiyama S, Fukui K: The Arabidopsis SDG4 contributes to the regulation of pollen tube growth by methylation of histone H3 lysines 4 and 36 in mature pollen. Dev Biol. 2008, 315: 355-368. 10.1016/j.ydbio.2007.12.016.View ArticlePubMedGoogle Scholar
- Berr A, McCallum EJ, Ménard R, Meyer D, Fuchs J, Dong A, Shen WH: Arabidopsis SET DOMAIN GROUP2 is required for H3K4 trimethylation and is crucial for both sporophyte and gametophyte development. Plant Cell. 2010, 22: 3232-3248. 10.1105/tpc.110.079962.PubMed CentralView ArticlePubMedGoogle Scholar
- Guo L, Yu Y, Law JA, Zhang X: SET DOMAIN GROUP2 is the major histone H3 lysine 4 trimethyltransferase in Arabidopsis. Proc Natl Acad Sci USA. 2010, 107: 18557-18562. 10.1073/pnas.1010478107.PubMed CentralView ArticlePubMedGoogle Scholar
- Ndamukong I, Chetram A, Saleh A, Avramova Z: Wall-modifying genes regulated by the Arabidopsis homolog of trithorax, ATX1: repression of the XTH33 gene as a test case. Plant J. 2009, 58: 541-553. 10.1111/j.1365-313X.2009.03798.x.View ArticlePubMedGoogle Scholar
- Arrowsmith DA, de Silva J: Characterisation of two tomato fruit-expressed cDNAs encoding xyloglucan endo-transglycosylase. Plant Mol Biol. 1995, 28: 391-403. 10.1007/BF00020389.View ArticlePubMedGoogle Scholar
- Berr A, Xu L, Gao J, Cognat V, Steinmetz A, Dong A, Shen WH: SET DOMAIN GROUP25 encodes a histone methyltransferase and is involved in FLOWERING LOCUS C activation and repression of flowering. Plant Physiol. 2009, 151: 1476-1485. 10.1104/pp.109.143941.PubMed CentralView ArticlePubMedGoogle Scholar
- Krause CD, Yang ZH, Kim YS, Lee JH, Cook JR, Pestka S: Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential. Pharmacol Ther. 2007, 113: 50-87. 10.1016/j.pharmthera.2006.06.007.View ArticlePubMedGoogle Scholar
- Yan D, Zhang Y, Niu L, Yuan Y, Cao X: Identification and characterization of two closely related histone H4 arginine 3 methyltransferases in Arabidopsis thaliana. Biochem J. 2007, 408: 113-121. 10.1042/BJ20070786.PubMed CentralView ArticlePubMedGoogle Scholar
- Scebba F, De Bastiani M, Bernacchia G, Andreucci A, Galli A, Pitto L: PRMT11: a new Arabidopsis MBD7 protein partner with arginine methyltransferase activity. Plant J. 2007, 52: 210-222. 10.1111/j.1365-313X.2007.03238.x.View ArticlePubMedGoogle Scholar
- Niu L, Lu F, Pei Y, Liu C, Cao X: Regulation of flowering time by the protein arginine methyltransferase AtPRMT10. EMBO Rep. 2007, 8: 1190-1195. 10.1038/sj.embor.7401111.PubMed CentralView ArticlePubMedGoogle Scholar
- Niu L, Zhang Y, Pei Y, Liu C, Cao X: Redundant requirement for a pair of PROTEIN ARGININE METHYLTRANSFERASE4 homologs for the proper regulation of Arabidopsis flowering time. Plant Physiol. 2008, 148: 490-503. 10.1104/pp.108.124727.PubMed CentralView ArticlePubMedGoogle Scholar
- Pei Y, Niu L, Lu F, Liu C, Zhai J, Kong X, Cao X: Mutations in the Type II protein arginine methyltransferase AtPRMT5 result in pleiotropic developmental defects in Arabidopsis. Plant Physiol. 2007, 144: 1913-1923. 10.1104/pp.107.099531.PubMed CentralView ArticlePubMedGoogle Scholar
- Zhang Z, Zhang S, Zhang Y, Wang X, Li D, Li Q, Yue M, Li Q, Zhang YE, Xu Y, Xue Y, Chong K, Bao S: Arabidopsis floral initiator SKB1 confers high salt tolerance by regulating transcription and pre-mRNA splicing through altering histone H4R3 and small nuclear ribonucleoprotein LSM4 methylation. Plant Cell. 2011, 23: 396-411. 10.1105/tpc.110.081356.PubMed CentralView ArticlePubMedGoogle Scholar
- Krichevsky A, Gutgarts H, Kozlovsky SV, Tzfira T, Sutton A, Sternglanz R, Mandel G, Citovsky V: C2H2 zinc finger-SET histone methyltransferase is a plant-specific chromatin modifier. Dev Biol. 2007, 303: 259-269. 10.1016/j.ydbio.2006.11.012.PubMed CentralView ArticlePubMedGoogle Scholar
- Krichevsky A, Zaltsman A, Kozlovsky SV, Tian GW, Citovsky V: Regulation of Root Elongation by Histone Acetylation in Arabidopsis. J Mol Biol. 2009, 385: 45-50. 10.1016/j.jmb.2008.09.040.PubMed CentralView ArticlePubMedGoogle Scholar
- Lu F, Li G, Cui X, Liu C, Wang XJ, Cao X: Comparative analysis of JmjC domain-containing proteins reveals the potential histone demethylases in Arabidopsis and rice. J Integr Plant Biol. 2008, 50: 886-896. 10.1111/j.1744-7909.2008.00692.x.View ArticlePubMedGoogle Scholar
- Noh B, Lee SH, Kim HJ, Yi G, Shin EA, Lee M, Jung KJ, Doyle MR, Amasino RM, Noh YS: Divergent roles of a pair of homologous jumonji/zinc-finger-class transcription factor proteins in the regulation of Arabidopsis flowering time. Plant Cell. 2004, 16: 2601-2613. 10.1105/tpc.104.025353.PubMed CentralView ArticlePubMedGoogle Scholar
- Isaacson T, Ohad I, Beyer P, Hirschberg J: Analysis in vitro of the enzyme CRTISO establishes a poly-cis-carotenoid biosynthesis pathway in plants. Plant Physiol. 2004, 136: 4246-4255. 10.1104/pp.104.052092.PubMed CentralView ArticlePubMedGoogle Scholar
- Liu YS, Gur A, Ronen G, Causse M, Damidaux R, Buret M, Hirschberg J, Zamir D: There is more to tomato fruit colour than candidate carotenoid genes. Plant Biotechnol J. 2003, 1: 195-207. 10.1046/j.1467-7652.2003.00018.x.View ArticlePubMedGoogle Scholar
- Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol. 1990, 215: 403-410.View ArticlePubMedGoogle Scholar
- Edgar RC: MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics. 2004, 5: 113-10.1186/1471-2105-5-113.PubMed CentralView ArticlePubMedGoogle Scholar
- Finn RD, Clements J, Eddy SR: HMMER web server: interactive sequence similarity searching. Nucleic Acids Res. 2011, 39: W29-W37. 10.1093/nar/gkr367.PubMed CentralView ArticlePubMedGoogle Scholar
- Schultz J, Milpetz F, Bork P, Ponting CP: SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci USA. 1998, 95: 5857-5864. 10.1073/pnas.95.11.5857.PubMed CentralView ArticlePubMedGoogle Scholar
- Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, Dufayard JF, Guindon S, Lefort V, Lescot M, Claverie JM, Gascuel O: Phylogeny fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008, 36: W465-W469. 10.1093/nar/gkn180.PubMed CentralView ArticlePubMedGoogle Scholar
- Felsenstein J: Confidence limits on phylogenies: an approach using the bootstrap. Evolution. 1985, 39: 783-791. 10.2307/2408678.View ArticleGoogle Scholar
- Pavlidis P, Noble WS: Matrix2png: a utility for visualizing matrix data. Bioinformatics. 2003, 19: 295-296. 10.1093/bioinformatics/19.2.295.View ArticlePubMedGoogle Scholar
- Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N, Braisted J, Klapa M, Currier T, Thiagarajan M, Sturn A, Snuffin M, Rezantsev A, Popov D, Ryltsov A, Kostukovich E, Borisovsky I, Liu Z, Vinsavich A, Trush V, Quackenbush J: TM4: a free, open-source system for microarray data management and analysis. Biotechniques. 2003, 34: 374-378.PubMedGoogle Scholar
- Saeed AI, Bhagabati NK, Braisted JC, Liang W, Sharov V, Howe EA, Li J, Thiagarajan M, White JA, Quackenbush J: TM4 microarray software suite. Methods Enzymol. 2006, 411: 134-193.View ArticlePubMedGoogle Scholar
- Eshed Y, Zamir D: A genomic library of Lycopersicon pennellii in L. esculentum: a tool for fine mapping of genes. Euphytica. 1994, 79: 175-179. 10.1007/BF00022516.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.