Ubiquitin E3 Ligase Ring1b/Rnf2 of Polycomb Repressive Complex 1 Contributes to Stable Maintenance of Mouse Embryonic Stem Cells

Polycomb repressive complex 1 (PRC1) core member Ring1b/Rnf2, with ubiquitin E3 ligase activity towards histone H2A at lysine 119, is essential for early embryogenesis. To obtain more insight into the role of Ring1b in early development, we studied its function in mouse embryonic stem (ES) cells. We...

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Vydáno v:	PloS one Ročník 3; číslo 5; s. e2235
Hlavní autoři:	van der Stoop, Petra, Boutsma, Erwin A., Hulsman, Danielle, Noback, Sonja, Heimerikx, Mike, Kerkhoven, Ron M., Voncken, J. Willem, Wessels, Lodewyk F. A., van Lohuizen, Maarten
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 21.05.2008 Public Library of Science (PLoS)
Témata:	Aberration Alkaline phosphatase Analysis Animals Bioinformatics Cancer Cell Biology/Gene Expression Cell cycle Cell interactions Cells, Cultured Cellular communication Chromatin Clonal deletion Cluster analysis Comparative analysis CpG Islands Deregulation Derepression Developmental Biology/Cell Differentiation Developmental Biology/Stem Cells Differentiation DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Drosophila Embryo cells Embryogenesis Embryonic growth stage Embryonic stem cells Embryonic Stem Cells - cytology Gene deletion Gene expression Gene Expression Profiling Gene regulation Gene silencing Genes Genetics and Genomics/Epigenetics Genetics and Genomics/Gene Expression Genomes Histone H2A Histones - metabolism Insects Ligases Lysine Mammals Mice Mice, Knockout Molecular Biology/Histone Modification Oct-4 protein Phosphatases Polycomb group proteins Polycomb Repressive Complex 1 Promoter Regions, Genetic Promoters Proteins Repressor Proteins RNA polymerase Stem cell transplantation Stem cells Transcription Transcription (Genetics) Transforming growth factors Ubiquitin Ubiquitin - metabolism Ubiquitin-protein ligase Ubiquitin-Protein Ligases Netherlands
ISSN:	1932-6203, 1932-6203
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Shrnutí:	Polycomb repressive complex 1 (PRC1) core member Ring1b/Rnf2, with ubiquitin E3 ligase activity towards histone H2A at lysine 119, is essential for early embryogenesis. To obtain more insight into the role of Ring1b in early development, we studied its function in mouse embryonic stem (ES) cells. We investigated the effects of Ring1b ablation on transcriptional regulation using Ring1b conditional knockout ES cells and large-scale gene expression analysis. The absence of Ring1b results in aberrant expression of key developmental genes and deregulation of specific differentiation-related pathways, including TGFbeta signaling, cell cycle regulation and cellular communication. Moreover, ES cell markers, including Zfp42/Rex-1 and Sox2, are downregulated. Importantly, retained expression of ES cell regulators Oct4, Nanog and alkaline phosphatase indicates that Ring1b-deficient ES cells retain important ES cell specific characteristics. Comparative analysis of our expression profiling data with previously published global binding studies shows that the genes that are bound by Ring1b in ES cells have bivalent histone marks, i.e. both active H3K4me3 and repressive H3K27me3, or the active H3K4me3 histone mark alone and are associated with CpG-'rich' promoters. However, deletion of Ring1b results in deregulation, mainly derepression, of only a subset of these genes, suggesting that additional silencing mechanisms are involved in repression of the other Ring1b bound genes in ES cells. Ring1b is essential to stably maintain an undifferentiated state of mouse ES cells by repressing genes with important roles during differentiation and development. These genes are characterized by high CpG content promoters and bivalent histone marks or the active H3K4me3 histone mark alone.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: Mv EB Pv JV. Performed the experiments: EB SN MH Pv DH JV. Analyzed the data: LW RK EB MH Pv. Wrote the paper: Mv Pv.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0002235