ATRX-mediated chromatin association of histone variant macroH2A1 regulates α-globin expression

Genes Dev. 2012 Mar 1;26(5):433-8. doi: 10.1101/gad.179416.111.

Kajan Ratnakumar ¹, Luis F Duarte, Gary LeRoy, Dan Hasson, Daniel Smeets, Chiara Vardabasso, Clemens Bönisch, Tianying Zeng, Bin Xiang, David Y Zhang, Haitao Li, Xiaowo Wang, Sandra B Hake, Lothar Schermelleh, Benjamin A Garcia, Emily Bernstein

Affiliations

Affiliation

1 Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.

PMID: 22391447 DOI: 10.1101/gad.179416.111

Abstract

The histone variant macroH2A generally associates with transcriptionally inert chromatin; however, the factors that regulate its chromatin incorporation remain elusive. Here, we identify the SWI/SNF helicase ATRX (α-thalassemia/MR, X-linked) as a novel macroH2A-interacting protein. Unlike its role in assisting H3.3 chromatin deposition, ATRX acts as a negative regulator of macroH2A's chromatin association. In human erythroleukemic cells deficient for ATRX, macroH2A accumulates at the HBA gene cluster on the subtelomere of chromosome 16, coinciding with the loss of α-globin expression. Collectively, our results implicate deregulation of macroH2A's distribution as a contributing factor to the α-thalassemia phenotype of ATRX syndrome.

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