Transcription factor EKLF (KLF1) recruitment of the histone chaperone HIRA is essential for β-globin gene expression

Shefali Soni, Nikolay Pchelintsev, Peter D. Adams, James J. Bieker

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 chap-erone can lead to tissue-restricted changes in chromatin components, structure, and transcription at specific genomic sites during differentiation.

Original languageEnglish
Pages (from-to)13337-13342
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number37
DOIs
StatePublished - 16 Sep 2014

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