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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Inoue D,Aihara H,Sato T,Mizusaki H,Doiguchi M,Higashi M,Imamura Y,Yoneda M,Miyanishi T,Fujii S,Okuda A,Nakagawa T,Ito Tdoi
10.1038/srep16567subject
Has Abstractpub_date
2015-11-16 00:00:00pages
16567issn
2045-2322pii
srep16567journal_volume
5pub_type
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