Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells

被引：65

作者：

Shiota, Hitoshi ^{[1
]}

Barral, Sophie ^{[1
]}

Buchou, Thierry ^{[1
]}

Tan, Minjia ^{[2
]}

Coute, Yohann ^{[3
]}

Charbonnier, Guillaume ^{[4
]}

Reynoird, Nicolas ^{[1
]}

Boussouar, Faycal ^{[1
]}

Gerard, Matthieu ^{[5
]}

Zhu, Mingrui ^{[2
]}

Bargier, Lisa ^{[4
]}

Puthier, Denis ^{[4
]}

Chuffart, Florent ^{[1
]}

Bourova-Flin, Ekaterina ^{[1
]}

Picaud, Sarah ^{[6
,7
]}

Filippakopoulos, Panagis ^{[6
,7
]}

Goudarzi, Afsaneh ^{[1
]}

Ibrahim, Ziad ^{[8
]}

Panne, Daniel ^{[8
,9
]}

Rousseaux, Sophie ^{[1
]}

Zhao, Yingming ^{[10
]}

Khochbin, Saadi ^{[1
]}

机构：

[1] Univ Grenoble Alpes, Inst Adv Biosci, Inserm U1209, CNRS UMR 5309, F-38700 Grenoble, France

[2] Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China

[3] Univ Grenoble Alpes, CEA, Inserm U1038, CEA,BIG BGE, F-38000 Grenoble, France

[4] Aix Marseille Univ, Inserm U1090, TGML, Platform IbiSA,TAGC, Marseille, France

[5] CEA, iBiTec S, F-91191 Gif Sur Yvette, France

[6] Struct Genom Consortium, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England

[7] Ludwig Inst Canc Res, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England

[8] EMBL Grenoble, BP 181,71 Ave Martyrs, F-38042 Grenoble 9, France

[9] Univ Leicester, Dept Mol & Cell Biol, Leicester Inst Struct & Chem Biol, Lancaster Rd, Leicester LE1 7RH, Leics, England

[10] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA

来源：

CELL REPORTS | 2018年 / 24卷 / 13期

基金：

英国惠康基金;

关键词：

MIDLINE CARCINOMA; NUCLEOSOME EVICTION; ACETYLATION; BROMODOMAIN; TRANSCRIPTION; BRDT; SPERMATOGENESIS; DIFFERENTIATION; PURIFICATION; TRANSITION;

D O I：

10.1016/j.celrep.2018.08.069

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome.

引用

页码：3477 / +

页数：17

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