title: Centromeric histone H2B monoubiquitination promotes noncoding transcription and chromatin integrity.
abstract: Functional centromeres are essential for proper cell division. Centromeres are established largely by epigenetic processes resulting in incorporation of the histone H3 variant CENP-A. Here, we demonstrate the direct involvement of H2B monoubiquitination, mediated by RNF20 in humans or Brl1 in Schizosaccharomyces pombe, in centromeric chromatin maintenance. Monoubiquinated H2B (H2Bub1) is needed for this maintenance, promoting noncoding transcription, centromere integrity and accurate chromosomal segregation. A transient pulse of centromeric H2Bub1 leads to RNA polymerase II-mediated transcription of the centromere's central domain, coupled to decreased H3 stability. H2Bub1-deficient cells have centromere cores that, despite their intact centromeric heterochromatin barriers, exhibit characteristics of heterochromatin, such as silencing histone modifications, reduced nucleosome turnover and reduced levels of transcription. In the H2Bub1-deficient cells, centromere functionality is hampered, thus resulting in unequal chromosome segregation. Therefore, centromeric H2Bub1 is essential for maintaining active centromeric chromatin.
authors: 1] Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. [2].
authors: Laia
authors: L
authors: Sadeghi
authors: 1] Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. [2].
authors: Lee
authors: L
authors: Siggens
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors: J Peter
authors: 0000000258636250
authors: JP
authors: Svensson
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors: Karl
authors: K
authors: Ekwall
mesh_terms: D002453:Cell Cycle; D002503:Centromere / Q000648:ultrastructure*; D002843:Chromatin / Q000737:chemistry*; D047369:Chromatin Immunoprecipitation; D020090:Chromosome Segregation; D002875:Chromosomes / Q000648:ultrastructure; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D015162:Micronucleus Tests; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C569203:Brr6 protein, S pombe; D002843:Chromatin; D006657:Histones; D008565:Membrane Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C506646:RNF20 protein, human; D044767:Ubiquitin-Protein Ligases