title: Transcriptional activation of polycomb-repressed genes by ZRF1.
abstract: 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.
authors.affiliation: Centre de Regulació Genòmica (CRG)/UPF, 08003 Barcelona, Spain.
authors.forename: Holger
authors.initials: H
authors.lastname: Richly
authors.forename: Luciana
authors.initials: L
authors.lastname: Rocha-Viegas
authors.forename: Joana Domingues
authors.initials: JD
authors.lastname: Ribeiro
authors.forename: Santiago
authors.initials: S
authors.lastname: Demajo
authors.forename: Gunes
authors.initials: G
authors.lastname: Gundem
authors.forename: Nuria
authors.initials: N
authors.lastname: Lopez-Bigas
authors.forename: Tekeya
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Sabine
authors.initials: S
authors.lastname: Rospert
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones; D015513:Oncogene Proteins / Q000378:metabolism*; D063146:Polycomb-Group Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation; D020298:U937 Cells; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D006657:Histones; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D063146:Polycomb-Group Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014452:Ubiquitins; C021645:chromatin conjugate protein A24