Fig. 6
DESR genes exhibiting opposing expression changes in regenerative vs. non-regenerative CNS identified inter-relationships among genes involved in cellular metabolism, post-transcriptional and epigenetic gene regulation, and microtubule dynamics in successful vs. unsuccessful CNS axon regeneration. a DESR genes that exhibited opposing expression between the two regenerative tissues (R: tadpole SCI hindbrain & juvenile frog ONC eye) vs. the non-regenerative tissue (NR: juvenile frog SCI hindbrain), sorted by the functional categories of Fig. 4. Green and red indicate genes that were up- and down-regulated significantly, respectively, with injury in the two regenerative tissues (R); these also exhibited significant differential expression with injury in the non-regenerative, juvenile frog SCI hindbrain (NR), but in the opposing direction. Gene symbols correspond with their human orthologs, and S & L homeologs/paralogs are combined into a single listing (see the explanation in Fig. 5). b The protein-protein interaction network of the genes in (a), as predicted by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, v10.5). Fifty five per cent (18/33) of oppositely expressed genes between regenerative and non-regenerative tissues were interconnected through interacting functions and molecular interactions associated with the cytoskeleton, DNA methylation, mRNA translation, histones and their epigenetic modifications, and cellular metabolism. The image was generated by STRING (https: //string-db.org; confidence level, 0.300; K-means clustering, k = 5). There were 22 edges with a PPI (protein-protein interaction) enrichment p-value = 0.0005. Colors of edges refer to the type of evidence linking the corresponding proteins (see Edge Legend, lower left). Inter-cluster edges are represented as dashed-lines. The dotted square highlights genes directly involved in epigenetic regulation of gene expression at promoters and enhancers. JARID2, SUZ12, and EZH2 are components of Polycomb Repressive Complex 2 (PRC2). EZH2 also plays a role in targeting DNMT3 to DNA. JHDM1D (also known as KDM7) is a principal demethylase for H3K9 and H3K27, prominent sites that interact with PRC2. IDH1 is a metabolic enzyme that stimulates TET, the enzyme principally responsible for converting 5mC to 5hmC & 5C