Short H2A histone variants are expressed in cancer

Guo-Liang Chew, Marie Bleakley, Robert K. Bradley, Harmit S. Malik, Steven Henikoff, Antoine Molaro () and Jay Sarthy ()
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Guo-Liang Chew: National University of Singapore
Marie Bleakley: Fred Hutchinson Cancer Research Center
Robert K. Bradley: Fred Hutchinson Cancer Research Center
Harmit S. Malik: Fred Hutchinson Cancer Research Center
Steven Henikoff: Fred Hutchinson Cancer Research Center
Antoine Molaro: Fred Hutchinson Cancer Research Center
Jay Sarthy: Fred Hutchinson Cancer Research Center

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20707-x

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