Epigenomics of Neural Cells: REST-Induced Down- and Upregulation of Gene Expression in a Two-Clone PC12 Cell Model

Figure 4

Possible mechanisms of gene down- and upregulation in hrPC12 cells analyzed by ChIP-Seq enrichment and Roadmap Epigenomics datasets. (a) and (b) show downregulated (a) and upregulated (b) genes of hrPC12 cells, separated in the four subfamilies dependent on their possible mechanism of regulation and illustrated as box-whiskers in terms of median fold distribution of the hrPC12/wtPC12 log₂ ratios. Notice that the notches (median ratios) are approximately the same for the subfamilies of both the down- and upregulated genes except for the downregulated, possible REST and PRC regulated subfamily, whose median ratio is significantly lower than those of the other downregulated subfamilies, suggesting the combined repression by the REST and PRC repression systems. (c) and (d) illustrate the distribution in the four subfamilies of the same downregulated (c) and upregulated (d) genes as revealed by the ChIP-Seq (blue circles) and Roadmap Epigenomics (yellow circles) datasets. In the presentation of the results obtained by the two approaches, three gene subfamilies are named differently: the subfamily REST only in the ChIP-Seq is named H3K4me1 only in the Roadmap Epigenomics; REST and PRC are H3K4me1 and H3K27me3; PRC only is H3K27me3 only. Notice that the two target and the two nontarget subfamilies predominate among the downregulated and the upregulated genes, respectively. These differences appeared to be markedly reinforced in the Roadmap Epigenomics analyses. In the figure the differential gene distributions revealed by the two approaches are illustrated as gene redistributions of different relevance among the subfamilies, illustrated as arrows of various thicknesses (red in (c), green in (d)).