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

Cell. 2016 Jun 2;165(6):1389-1400. doi: 10.1016/j.cell.2016.04.031. Epub 2016 May 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • DNA Methylation
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation
  • Histones / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / cytology
  • Lysine / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism
  • Promoter Regions, Genetic*


  • Histones
  • Polycomb Repressive Complex 2
  • Lysine