Short H2A histone variants are expressed in cancer.

Szczegóły
Abstrakt

Tytuł:: Short H2A histone variants are expressed in cancer.
Autorzy:: Chew GL; The Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Bleakley M; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Bradley RK; Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Malik HS; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Henikoff S; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Molaro A; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. .; Genetics, Reproduction and Development (GReD) Institute, Université Clermont Auvergne, Clermont-Ferrand, France. .
Sarthy J; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. .
Źródło:: Nature communications [Nat Commun] 2021 Jan 20; Vol. 12 (1), pp. 490. Date of Electronic Publication: 2021 Jan 20.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Gene Expression Regulation, Neoplastic*
Histones/*genetics
Histones/*metabolism
Neoplasms/*genetics
Neoplasms/*metabolism
Alternative Splicing ; Animals ; Chromatin ; Epigenomics ; Female ; Genomics ; Humans ; Nucleosomes ; Placenta ; Pregnancy ; Up-Regulation
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Grant Information:: R01 GM074108 United States GM NIGMS NIH HHS; United States HHMI Howard Hughes Medical Institute
Substance Nomenclature:: 0 (Chromatin)
0 (Histones)
0 (Nucleosomes)
Entry Date(s):: Date Created: 20210121 Date Completed: 20210201 Latest Revision: 20240330
Update Code:: 20240330
PubMed Central ID:: PMC7817690
DOI:: 10.1038/s41467-020-20707-x
PMID:: 33473122
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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.

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