Dzip3 regulates developmental genes in mouse embryonic stem cells by reorganizing 3D chromatin conformation

Autor: Yuko Imamura, Masamichi Doiguchi, Miki Higashi, Satoshi Fujii, Takeya Nakagawa, Daishi Inoue, Tatsuharu Sato, Akihiko Okuda, Takashi Ito, Mitsuhiro Yoneda, Hirofumi Mizusaki, Takayuki Miyanishi, Hitoshi Aihara
Rok vydání: 2015
Předmět:
Zdroj: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/srep16567
Popis: 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.
Scientific Reports, 5, 16567; 2015
Databáze: OpenAIRE