EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells

被引：81

作者：

Ragazzini, Roberta ^{[1
]}

Perez-Palacios, Raquel ^{[1
]}

Baymaz, Irem H. ^{[2
]}

Diop, Seynabou ^{[1
]}

Ancelin, Katia ^{[1
]}

Zielinski, Dina ^{[1
,3
]}

Michaud, Audrey ^{[1
]}

Givelet, MaeIle ^{[4
]}

Borsos, Mate ^{[5
,6
]}

Aflaki, Setareh ^{[1
]}

Legoix, Patricia ^{[7
]}

Jansen, Pascal W. T. C. ^{[2
]}

Servant, Nicolas ^{[1
,3
]}

Torres-Padilla, Maria-Elena ^{[5
,6
]}

Bourc'his, Deborah ^{[1
]}

Fouchet, Pierre ^{[4
]}

Vermeulen, Michiel ^{[2
]}

Margueron, Raphael ^{[1
]}

机构：

[1] Sorbonne Univ, PSL Res Univ, INSERM U934, Inst Curie,CNRS UMR3215, 26 Rue Ulm, F-75005 Paris, France

[2] Radboud Univ Nijmegen, Oncode Inst, Radboud Inst Mol Life Sci, Fac Sci,Dept Mol Biol, Route 274,M850-03-87 Geert Grootepl 28, NL-6525 GA Nijmegen, Netherlands

[3] Mines ParisTech, INSERM U900, 26 Rue Ulm, Paris, France

[4] INSERM U967, Lab Cellules Souches Germinales, Inst Radiobiol Cellulaire & Mol, Commissariat Energie Atom & Energies Alternat, F-92260 Fontenay Aux Roses, France

[5] Helmholtz Zentrum Munchen, Inst Epigenet & Stem Cells IES, D-81377 Munich, Germany

[6] Ludwig Maximilians Univ Munchen, Fac Biol, D-81377 Munich, Germany

[7] Curie Inst, ICGex Next Generat Sequencing Platform, 26 Rue Ulm, Paris, France

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

EMBRYONIC STEM-CELLS; CHROMATIN DYNAMICS; PRC2; MOUSE; METHYLATION; PROTEIN; TRANSCRIPTOME; REVEALS; AEBP2; DNA;

D O I：

10.1038/s41467-019-11800-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Polycomb group of proteins is required for the proper orchestration of gene expression due to its role in maintaining transcriptional silencing. It is composed of several chromatin modifying complexes, including Polycomb Repressive Complex 2 (PRC2), which deposits H3K27me2/3. Here, we report the identification of a cofactor of PRC2, EZHIP (EZH1/2 Inhibitory Protein), expressed predominantly in the gonads. EZHIP limits the enzymatic activity of PRC2 and lessens the interaction between the core complex and its accessory subunits, but does not interfere with PRC2 recruitment to chromatin. Deletion of Ezhip in mice leads to a global increase in H3K27me2/3 deposition both during spermatogenesis and at late stages of oocyte maturation. This does not affect the initial number of follicles but is associated with a reduction of follicles in aging. Our results suggest that mature oocytes Ezhip-/- might not be fully functional and indicate that fertility is strongly impaired in Ezhip-/- females. Altogether, our study uncovers EZHIP as a regulator of chromatin landscape in gametes.

引用

页数：18

共 69 条

[1] Reciprocal interactions of human C10orf12 and C17orf96 with PRC2 revealed by BioTAP-XL cross-linking and affinity purification [J].