Short H2A histone variants are expressed in cancer

• DOI: 10.1038/s41467-020-20707-x
• Publication Date: 2021-01-20T11:03:53Z
• Authors: Guo-Liang Chew; Marie Bleakley; Robert K. Bradley; Harmit S. Malik; Steven Henikoff; Antoine Molaro; Jay Sarthy
• Keywords: Epigenomics; 0301 basic medicine; [SDV]Life Sciences [q-bio]; Science; Placenta; Article; Histones; 03 medical and health sciences; Pregnancy; Neoplasms; [SDV.BDD] Life Sciences [q-bio]/Development Biology; Animals; Humans; [SDV.BDD]Life Sciences [q-bio]/Development Biology; [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology; Q; Genomics; Chromatin; Nucleosomes; Up-Regulation; 3. Good health; [SDV] Life Sciences [q-bio]; Gene Expression Regulation, Neoplastic; Alternative Splicing; Female; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

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 alternate splicing. Here, we show that sH2As innately possess features similar to recurrent oncohistone mutations instability. Through analyses existing cancer genomics datasets, find aberrant sH2A upregulation a broad array cancers, which manifest splicing patterns consistent global destabilization. We posit short H2As class "ready-made" oncohistones, whose inappropriate expression contributes dysfunction cancer.