title: Transcription factor EKLF (KLF1) recruitment of the histone chaperone HIRA is essential for β-globin gene expression.
abstract: The binding of chromatin-associated proteins and incorporation of histone variants correlates with alterations in gene expression. These changes have been particularly well analyzed at the mammalian β-globin locus, where transcription factors such as erythroid Krüppel-like factor (EKLF), which is also known as Krüppel-like factor 1 (KLF1), play a coordinating role in establishing the proper chromatin structure and inducing high-level expression of adult β-globin. We had previously shown that EKLF preferentially interacts with histone H3 and that the H3.3 variant is differentially recruited to the β-globin promoter. We now find that a novel interaction between EKLF and the histone cell cycle regulation defective homolog A (HIRA) histone chaperone accounts for these effects. HIRA is not only critical for β-globin expression but is also required for activation of the erythropoietic regulators EKLF and GATA binding protein 1 (GATA1). Our results provide a mechanism by which transcription factor-directed recruitment of a generally expressed histone chaperone can lead to tissue-restricted changes in chromatin components, structure, and transcription at specific genomic sites during differentiation.
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029;
authors.forename: Shefali
authors.initials: S
authors.lastname: Soni
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, Scotland;
authors.forename: Nikolay
authors.initials: N
authors.lastname: Pchelintsev
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, Scotland; Beatson Institute for Cancer Research, Glasgow G61 1BD, Scotland; and.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Adams
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029; Black Family Stem Cell Institute, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029 james.bieker@mssm.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Bieker
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D041905:Erythroid Cells / Q000378:metabolism; D004920:Erythropoiesis; D005786:Gene Expression Regulation; D056488:Histone Chaperones / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D016335:Zinc Fingers; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C484187:Hira protein, mouse; D056488:Histone Chaperones; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D055544:beta-Globins; C080774:erythroid Kruppel-like factor