Transcriptional activation of polycomb-repressed genes by ZRF1

Nature. 2010 Dec 23;468(7327):1124-8. doi: 10.1038/nature09574.


Covalent modification of histones is fundamental in orchestrating chromatin dynamics and transcription. One example of such an epigenetic mark is the mono-ubiquitination of histones, which mainly occurs at histone H2A and H2B. Ubiquitination of histone H2A has been implicated in polycomb-mediated transcriptional silencing. However, the precise role of the ubiquitin mark during silencing is still elusive. Here we show in human cell lines that ZRF1 (zuotin-related factor 1) is specifically recruited to histone H2A when it is ubiquitinated at Lys 119 by means of a novel ubiquitin-interacting domain that is located in the evolutionarily conserved zuotin domain. At the onset of differentiation, ZRF1 specifically displaces polycomb-repressive complex 1 (PRC1) from chromatin and facilitates transcriptional activation. A genome-wide mapping of ZRF1, RING1B and H2A-ubiquitin targets revealed its involvement in the regulation of a large set of polycomb target genes, emphasizing the key role ZRF1 has in cell fate decisions. We provide here a model of the molecular mechanism of switching polycomb-repressed genes to an active state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromatin / metabolism
  • Chromosome Mapping
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Gene Silencing*
  • HEK293 Cells
  • Histones / metabolism
  • Humans
  • Models, Biological
  • Molecular Chaperones
  • Oncogene Proteins / metabolism*
  • Polycomb-Group Proteins
  • RNA-Binding Proteins
  • Repressor Proteins / metabolism*
  • Transcriptional Activation*
  • U937 Cells
  • Ubiquitins / metabolism


  • Chromatin
  • DNA-Binding Proteins
  • DNAJC2 protein, human
  • Histones
  • Molecular Chaperones
  • Oncogene Proteins
  • Polycomb-Group Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • Ubiquitins
  • chromatin conjugate protein A24