Control of developmental regulators by Polycomb in human embryonic stem cells

Cell. 2006 Apr 21;125(2):301-13. doi: 10.1016/j.cell.2006.02.043.

Abstract

Polycomb group proteins are essential for early development in metazoans, but their contributions to human development are not well understood. We have mapped the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire nonrepeat portion of the genome in human embryonic stem (ES) cells. We found that SUZ12 is distributed across large portions of over two hundred genes encoding key developmental regulators. These genes are occupied by nucleosomes trimethylated at histone H3K27, are transcriptionally repressed, and contain some of the most highly conserved noncoding elements in the genome. We found that PRC2 target genes are preferentially activated during ES cell differentiation and that the ES cell regulators OCT4, SOX2, and NANOG cooccupy a significant subset of these genes. These results indicate that PRC2 occupies a special set of developmental genes in ES cells that must be repressed to maintain pluripotency and that are poised for activation during ES cell differentiation.

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Humans
  • Multiprotein Complexes
  • Nuclear Proteins
  • Oligonucleotide Array Sequence Analysis
  • Polycomb Repressive Complex 2
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Protein Subunits
  • SUZ12 protein, human
  • Transcription Factors
  • Polycomb Repressive Complex 2
  • RNA Polymerase II