Transcriptional activation of polycomb-repressed genes by ZRF1.
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.
Mesh Terms:
Cell Line, Tumor, Chromatin, Chromosome Mapping, DNA-Binding Proteins, Gene Expression Regulation, Gene Silencing, HEK293 Cells, Histones, Humans, Models, Biological, Oncogene Proteins, Repressor Proteins, Transcriptional Activation, U937 Cells, Ubiquitins
Cell Line, Tumor, Chromatin, Chromosome Mapping, DNA-Binding Proteins, Gene Expression Regulation, Gene Silencing, HEK293 Cells, Histones, Humans, Models, Biological, Oncogene Proteins, Repressor Proteins, Transcriptional Activation, U937 Cells, Ubiquitins
Nature
Date: Dec. 23, 2010
PubMed ID: 21179169
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