Publication Date:
2010-12-24
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richly, Holger -- Rocha-Viegas, Luciana -- Ribeiro, Joana Domingues -- Demajo, Santiago -- Gundem, Gunes -- Lopez-Bigas, Nuria -- Nakagawa, Tekeya -- Rospert, Sabine -- Ito, Takashi -- Di Croce, Luciano -- England -- Nature. 2010 Dec 23;468(7327):1124-8. doi: 10.1038/nature09574.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre de Regulacio Genomica (CRG)/UPF, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179169" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line, Tumor
;
Chromatin/metabolism
;
Chromosome Mapping
;
DNA-Binding Proteins/*metabolism
;
Gene Expression Regulation
;
*Gene Silencing
;
HEK293 Cells
;
Histones/metabolism
;
Humans
;
Models, Biological
;
Oncogene Proteins/*metabolism
;
Polycomb-Group Proteins
;
Repressor Proteins/*metabolism
;
*Transcriptional Activation
;
U937 Cells
;
Ubiquitins/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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