Fig. 1: Repressive complexes and associated epigenetic marks acting on DMS germline genes in pESCs. | Nature Communications

Fig. 1: Repressive complexes and associated epigenetic marks acting on DMS germline genes in pESCs.

From: Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing

Fig. 1

a Three repressive complexes (I–III) which act on a subset of germline genes have been identified previously in primed (serum-grown) ESCs (pESCs) and/or somatic cells. The promoter regions of these genes are bound by heterodimers of the transcription factors MGA and MAX, which are recruited to E-Box sites as well as E2F6, which binds to E2F sites. Complex I: The de novo DNA methyltransferase DNMT3B is recruited to germline genes via MGA/MAX and/or E2F6. Complex II: The lysine (K)MTase SETDB1, which deposits H3K9me3, is recruited to germline genes dependent upon MAX. SETDB1 is known to interact with the co-repressor TRIM28. HP1 proteins are recruited to H3K9me3 marked regions. Complex III: The non-canonical PRC1 complex PRC1.6, including PCGF6, L3MBTL2, RYBP, HP1β/γ, and RING1A/B subunits, is recruited to germline genes by MGA/MAX and E2F6. RING1A/B deposit H2AK119ub1, which in turn is recognized by the PRC2 complex, promoting H3K27me3 deposition. The KMTase G9A/EHMT2 was previously reported to associate with PRC1.6 complex via L3MBTL245. b Scatterplot showing the relationship between the enrichment (RPKM) of MGA or E2F6 (dot size) and % DNAme (TSS −0.9/+0.4 kb). c Screenshots of ChIP-seq and WGBS tracks showing RPM values of the indicated subunits of each of the complexes described in (a) as well as histone PTMs and % DNAme at the TSSs (±3 kb) of genes in pESCs. E-Box motifs and E2F motifs are shown as arrowheads. Annotated CpG islands (CGIs) are also shown. d, e Scatterplots showing the relationship between (d) MGA and H3K9me3, or (e) MGA and H2AK119ub1 (RPKM), around the TSSs (±2 kb) of all annotated genes in pESCs. In panels (b, d, e), all genes are labeled in (gray) while the 137 DMS germline genes upregulated in Dnmt3a/3b DKO embryonic day 8.5 embryos12 and subset categorized as germline “genome-defence” (GGD) genes (also upregulated in DNAme-deficient MEFs18) are labeled in blue and red, respectively. Control genes Hoxb1 (a canonical PRC1/2 target), Pou5f1 (an actively transcribed gene), and Peg3 (a TRIM28 target) are labeled in black. See Supplementary Data 2 for details of published datasets analyzed.

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