Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells.
Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells.
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DOI：
10.1016/j.cell.2016.04.031
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发表时间：
2016-06-02
期刊：
影响因子：
64.5
通讯作者：
Shivdasani RA
中科院分区：
文献类型：
--
作者：
Jadhav U;Nalapareddy K;Saxena M;O'Neill NK;Pinello L;Yuan GC;Orkin SH;Shivdasani RA
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 find 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.
