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Table 4 Example hypotheses inspired by DMR findings

From: Genome-wide effects of social status on DNA methylation in the brain of a cichlid fish, Astatotilapia burtoni

Finding(s)

Hypothesis

Top DMRs in ERAD genes, e.g. ubxn4, possible connections to AR

ERAD modulation by AR necessary to stabilize neural circuits that include GnRH1 and somatostatin cells after social ascent.

cacna2d2 DMR upstream of lncRNA has AR binding site & CNE

lncRNA regulates cacna2d2 under specific control of AR in the context of altered Ca2+ currents in cells that recently changed size

DMR in erbb4 and interactors, DMR genes in VIP gene clusters

erbb4 signaling in VIP cells modulates neural circuit changes related to reproductive capability, D fish lacking erbb4 may struggle to mate or maintain status

DMRs in nr3c1, nos1ap, GABA/glutamate/endocannabinoid pathways

GR stimulation of endocannabinoids/NO selectively regulates excitatory/inhibitory signals onto VIP and AVT cells, based on social status

Intronic DMR in nr3c1

DNA methylation governs the expression of specific nr3c1 isoforms, driving status-specific cortisol sensitivity

  1. This table summarizes some results from this study in column 1 and hypotheses they inspired in column 2. This is by no means an exhaustive list, but we think these represent some provocative but testable ideas that would not have arisen if not for this whole-genome scan of methylation patterns in the context of A. burtoni social status