title: The flip side of the coin: role of ZRF1 and histone H2A ubiquitination in transcriptional activation.
abstract: We have recently reported that the protein ZRF1 specifically binds to monoubiquitinated histone H2A and derepresses Polycomb target genes at the onset of cellular differentiation. Our results suggest that ZRF1 exerts its function in a two-step mechanism, by initially displacing the Polycomb-repressive complex 1 (PRC1) from chromatin and subsequently acting together with histone H2A-specific deubiquitinases to facilitate transcriptional activation of its target genes. These findings demonstrate an ambiguity of the epigenetic monoubiquitin mark at histone H2A. Once considered to be a hallmark of gene silencing, it is now clear that this mark can also be utilized as a recruitment platform for proteins engaged in gene activation. Genome-wide analyses demonstrate that ZRF1 is recruited to typical Polycomb target genes, thereby putting it in a position to have an impact on differentiation and animal development. This molecular mechanism for ZRF1 may represent one of the first steps in switching silenced genes to a transcriptionally active state. We discuss here our recent findings in the light of progress made in understanding Polycomb-mediated silencing.
authors.affiliation: Centre de Regulació Genòmica (CRG), Parc de Recerca Biomèdica, Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Holger
authors.initials: H
authors.lastname: Richly
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006657:Histones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016601:RNA-Binding Proteins; D016196:S Phase; D015533:Transcriptional Activation; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D006657:Histones; D018832:Molecular Chaperones; D015513:Oncogene Proteins; C116662:PRC1 protein, human; D016601:RNA-Binding Proteins