title: Dzip3 regulates developmental genes in mouse embryonic stem cells by reorganizing 3D chromatin conformation.
abstract: In mouse embryonic stem (mES) cells, ubiquitylation of histone H2A lysine 119 represses a large number of developmental genes and maintains mES cell pluripotency. It has been suggested that a number of H2A ubiquitin ligases as well as deubiquitylases and related peptide fragments contribute to a delicate balance between self-renewal and multi-lineage differentiation in mES cells. Here, we tested whether known H2A ubiquitin ligases and deubiquitylases are involved in mES cell regulation and discovered that Dzip3, the E3 ligase of H2AK119, represses differentiation-inducible genes, as does Ring1B. The two sets of target genes partially overlapped but had different spectra. We found that Dzip3 represses gene expression by orchestrating changes in 3D organization, in addition to regulating ubiquitylation of H2A. Our results shed light on the epigenetic mechanism of transcriptional regulation, which depends on 3D chromatin reorganization to regulate mES cell differentiation.
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.|Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Daishi
authors.initials: D
authors.lastname: Inoue
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Aihara
authors.affiliation: Department of Pediatrics, Nagasaki University Hospital.
authors.forename: Tatsuharu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mizusaki
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Doiguchi
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.
authors.forename: Miki
authors.initials: M
authors.lastname: Higashi
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Environmental Science, Nagasaki University.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyanishi
authors.affiliation: Kyushu Institute of Technology, Fukuoka 820-8502, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Division of Developmental Biology, Saitama Medical School Research Center for Genomic Medicine.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuda
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.
authors.forename: Takeya
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Biochemistry, Nagasaki University School of Medicine.|Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D015870:Gene Expression; D050437:Genes, Developmental; D006657:Histones / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000201:enzymology*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D006657:Histones; D016601:RNA-Binding Proteins; D044767:Ubiquitin-Protein Ligases; C000610638:Dzip3 protein, mouse