Figure 4. The Transition from HF-SCs to HF-TACs Involves PcG-Mediated Gene Repression of Key Stemness Genes.
(A) Schematic of the two cell populations used for the comparisons described in this Figure. (Right) Global histone methylation patterns of chromatin from qHF-SCs and matrix HF-TACs. Note paucity of H3K4me3+H3K27me3 marked genes (yellow bar). (B) (Left) 12.5% of HF-SC signature genes are PcG-repressed in HF-TACs (red). (Right) mRNA expression (Log2) of HF-SC signature genes marked by H3K4me3+H3K79me2 is much greater in qHF-SCs than equivalently marked genes in HF-TACs. H3K4me3+H3K79me2 marked genes (blue) are more highly expressed than genes marked only by H3K4me3 (green). (C) How H3 methylation patterns of qHF-SC chromatin change during the transition to HF-TACs. Genes (total numbers indicated above each bar) displaying a particular chromatin state in qHF-SCs (indicated below each bar) were analyzed for their H3 methylation patterns in HF-TACs (color-coded as indicated). Note that only a small number of genes repressed or bivalent in qHF-SCs are now active in HF-TACs. Note also that some genes marked by H3K4me3 in qHF-SCs are now H3K27me3-repressed in HF-TACs. (D) Gene ontologies and associated examples of HF-SC signature genes that go from an active to repressed state in HF-TACs. Note that key HF-SC TF genes are among this shortlist. (E) Box and whisker plots of H3K4me3 and H3K79me2 peak intensities over key HF-SC genes vs housekeeping/control genes (examples provided beneath the plots) as analyzed both in qHF-SCs and in HF-TACs. Note that peak intensities are greatest for key genes in qHF-SCs, and that marked reductions in these chromatin marks occurs upon transition to the TA state. See also Figure S2 & Table S5.