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

Genes & Development, 2012, doi: 10.1101/gad.179416.111, 26: 433-438 published on 01.03.2012
Genes & Development, online article
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 (alpha-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 ofmacroH2A’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 alpha-globin expression. Collectively, our results implicate deregulation of macroH2A’s distribution as a contributing factor to the alpha-thalassemia phenotype of ATRX syndrome.  

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