ATRX-mediated chromatin association of histone variant macroH2A1 regulates α-globin expression
- Kajan Ratnakumar1,2,
- Luis F. Duarte1,2,
- Gary LeRoy3,10,
- Dan Hasson1,4,10,
- Daniel Smeets5,10,
- Chiara Vardabasso1,2,
- Clemens Bönisch6,
- Tianying Zeng7,
- Bin Xiang8,
- David Y. Zhang9,
- Haitao Li8,
- Xiaowo Wang7,
- Sandra B. Hake6,
- Lothar Schermelleh5,11,
- Benjamin A. Garcia3 and
- Emily Bernstein1,2,12
- 1Department of Oncological Sciences,
- 2Department of Dermatology, Mount Sinai School of Medicine, New York, New York 10029, USA;
- 3Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA;
- 4Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA;
- 5Department of Biology II, Ludwig Maximilians University Munich, 82152 Martinsried, Germany;
- 6Munich Center for Integrated Protein Science, Adolf-Butenandt Institute, Ludwig-Maximilians University, 80336 Munich, Germany;
- 7MOE Key Laboratory of Bioinformatics, Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, China;
- 8Center for Structural Biology, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;
- 9Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA
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↵10 These authors contributed equally to this work.
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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Footnotes
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↵12 Corresponding author.
E-mail emily.bernstein{at}mssm.edu.
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.179416.111.
- Received September 20, 2011.
- Accepted January 30, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press
