Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells

作者：Jadhav Unmesh; Nalapareddy Kodandaramireddy; Saxena Madhurima; O'Neill Nicholas K; Pinello Luca; Yuan Guo Cheng; Orkin Stuart H; Shivdasani Ramesh A^*

来源：Cell, 2016, 165(6): 1389-1400.

DOI：10.1016/j.cell.2016.04.031

Bivalent promoters in embryonic stem cells (ESCs) carry methylation marks on two lysine residues, K4 and K27, in histone3 (H3). K4me2/3 is generally considered to promote transcription, and Polycomb Repressive Complex 2 (PRC2) places K27me3, which is erased at lineage-restricted genes when ESCs differentiate in culture. Molecular defects in various PRC2 null adult tissues lack a unifying explanation. We found that epigenomes in adult mouse intestine and other self-renewing tissues show fewer and distinct bivalent promoters compared to ESCs. Groups of tissue-specific genes that carry bivalent marks are repressed, despite the presence of promoter H3K4me2/3. These are the predominant genes de-repressed in PRC2-deficient adult cells, where aberrant expression is proportional to the H3K4me2/3 levels observed at their promoters in wild-type cells. Thus, in adult animals, PRC2 specifically represses genes with acquired, tissue-restricted promoter bivalency. These findings provide new insights into specificity in chromatin-based gene regulation.

• 出版日期2016-6-2