期刊
CELL
卷 165, 期 6, 页码 1389-1400出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.04.031
关键词
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资金
- Intestinal Stem Cell Consortium of the NIDDK [U01DK103152]
- NIAID
- DFCI-Novartis Drug Discovery Program
- NIH [R01DK081113, R01HG005085, F32DK103453, K99HG008399, P50CA127003]
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.
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