Author Information
1The Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
2Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
3Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
4Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
5Department of Genome Sciences, University of Washington, Seattle, WA, USA.
6Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
7Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. antoine.molaro@uca.fr.
8Genetics, Reproduction and Development (GReD) Institute, Université Clermont Auvergne, Clermont-Ferrand, France. antoine.molaro@uca.fr.
9Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jsarthy@fredhutch.org.
Abstract:
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.
PMID: 33473122 PMCID: PMC7817690 DOI: 10.1038/s41467-020-20707-x