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

Sci Rep. 2015 Nov 16;5:16567

Daishi Inoue ¹ , Hitoshi Aihara ² , Tatsuharu Sato ³ , Hirofumi Mizusaki ² , Masamichi Doiguchi ² ,

Daishi Inoue ¹ , Hitoshi Aihara ² , Tatsuharu Sato ³ , Hirofumi Mizusaki ² , Masamichi Doiguchi ² , Miki Higashi ² , Yuko Imamura ² , Mitsuhiro Yoneda ² , Takayuki Miyanishi ⁴ , Satoshi Fujii ⁵ , Akihiko Okuda ⁶ , Takeya Nakagawa ² , Takashi Ito ¹

+ et al

Author information

¹ Nagasaki University Graduate School of Biomedical Sciences.
² Department of Biochemistry, Nagasaki University School of Medicine.
³ Department of Pediatrics, Nagasaki University Hospital.
⁴ Department of Environmental Science, Nagasaki University.
⁵ Kyushu Institute of Technology, Fukuoka 820-8502, Japan.
⁶ Division of Developmental Biology, Saitama Medical School Research Center for Genomic Medicine.

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摘要

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.

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原始数据

保存测序数据

Sample name	Organism	Experiment title	Sample type	Library instrument	Attributes
Sample name	Organism	Experiment title	Sample type	Library instrument	cell type	genotype	passages	source name	strain
ubH2A_ChIPSeq	Mus musculus	GSM1847175: ubH2A_ChIPSeq; Mus musculus; ChIP-Seq	ChIP-Seq	Illumina MiSeq	embryonic stem cell		passage 3-5	ESCs_ChIP-seq	129/Ola
Dzip3_ChIPSeq	Mus musculus	GSM1847174: Dzip3_ChIPSeq; Mus musculus; ChIP-Seq	ChIP-Seq	Illumina MiSeq	embryonic stem cell		passage 3-5	ESCs_ChIP-seq	129/Ola
Ring1B_ChIPSeq	Mus musculus	GSM1847173: Ring1B_ChIPSeq; Mus musculus; ChIP-Seq	ChIP-Seq	Illumina MiSeq	embryonic stem cell		passage 3-5	ESCs_ChIP-seq	129/Ola
input DNA	Mus musculus	GSM1847172: input DNA; Mus musculus; ChIP-Seq	ChIP-Seq	Illumina MiSeq	embryonic stem cell		passage 3-5	ESCs_input	129/Ola
Dzip3-KD rep2	Mus musculus	GSM1847171: Dzip3-KD rep2; Mus musculus; RNA-Seq	RNA-Seq	Illumina MiSeq	embryonic stem cell	Dzip3 knockdown	passage 3-5	Dzip3-KD_ESCs	129/Ola