title: ATRX-mediated chromatin association of histone variant macroH2A1 regulates α-globin expression.
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.
authors.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Kajan
authors.initials: K
authors.lastname: Ratnakumar
authors.forename: Luis F
authors.initials: LF
authors.lastname: Duarte
authors.forename: Gary
authors.initials: G
authors.lastname: LeRoy
authors.forename: Dan
authors.initials: D
authors.lastname: Hasson
authors.forename: Daniel
authors.initials: D
authors.lastname: Smeets
authors.forename: Chiara
authors.initials: C
authors.lastname: Vardabasso
authors.forename: Clemens
authors.initials: C
authors.lastname: Bönisch
authors.forename: Tianying
authors.initials: T
authors.lastname: Zeng
authors.forename: Bin
authors.initials: B
authors.lastname: Xiang
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Xiaowo
authors.initials: X
authors.lastname: Wang
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Hake
authors.forename: Lothar
authors.initials: L
authors.lastname: Schermelleh
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.forename: Emily
authors.initials: E
authors.lastname: Bernstein
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D041905:Erythroid Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D038901:X-Linked Intellectual Disability / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D000075924:X-linked Nuclear Protein; D055542:alpha-Globins / Q000235:genetics* / Q000378:metabolism*; D017085:alpha-Thalassemia / Q000473:pathology
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D055542:alpha-Globins; C120756:macroH2A histone; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein