Short H2A histone variants are expressed in cancer

被引：28

作者：

Chew, Guo-Liang ^{[1
]}

Bleakley, Marie ^{[2
]}

Bradley, Robert K. ^{[3
,4
,5
]}

Malik, Harmit S. ^{[4
,6
]}

Henikoff, Steven ^{[4
,6
]}

Molaro, Antoine ^{[4
,7
]}

Sarthy, Jay ^{[4
]}

机构：

[1] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore

[2] Fred Hutchinson Canc Res Ctr, Clin Res Div, 1124 Columbia St, Seattle, WA 98104 USA

[3] Fred Hutchinson Canc Res Ctr, Computat Biol Program, Publ Hlth Sci Div, 1124 Columbia St, Seattle, WA 98104 USA

[4] Fred Hutchinson Canc Res Ctr, Basic Sci Div, 1124 Columbia St, Seattle, WA 98104 USA

[5] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[6] Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Seattle, WA 98104 USA

[7] Univ Clermont Auvergne, Genet Reprod & Dev GReD Inst, Clermont Ferrand, France

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; MUTATIONS; H2A.BBD; NUCLEOSOME; STABILITY; SEQUENCE; MOUSE;

D O I：

10.1038/s41467-020-20707-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：

Short H2A (sH2A) histone variants are primarily expressed in the testes of placental mammals. Their incorporation into chromatin is associated with nucleosome destabilization and modulation of alternate splicing. Here, we show that sH2As innately possess features similar to recurrent oncohistone mutations associated with nucleosome instability. Through analyses of existing cancer genomics datasets, we find aberrant sH2A upregulation in a broad array of cancers, which manifest splicing patterns consistent with global nucleosome destabilization. We posit that short H2As are a class of "ready-made" oncohistones, whose inappropriate expression contributes to chromatin dysfunction in cancer. Short H2A variants are testis-specific histones that destabilize nucleosomes during spermatogenesis. In this study, the authors show that these variants are expressed in an array of different cancers and identify splicing changes associated with nucleosome instability in these malignancies.

引用

页数：9

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