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P/CAF‐mediated acetylation regulates the function of the basic helix–loop–helix transcription factor TAL1/SCL
Author(s) -
Huang Suming,
Qiu Yi,
Shi Yubin,
Xu Zhixiong,
Brandt Stephen J.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.24.6792
Subject(s) - acetylation , biology , transcription factor , histone acetyltransferase , histone deacetylase , repressor , histone , microbiology and biotechnology , p300 cbp transcription factors , transcription (linguistics) , basic helix loop helix , dna binding protein , biochemistry , dna , histone acetyltransferases , gene , linguistics , philosophy
The basic helix–loop–helix transcription factor TAL1 (or SCL) is a critical regulator of hematopoietic and vascular development and is misexpressed in the majority of patients with T‐cell acute lymphoblastic leukemia. We found previously that TAL1 could interact with transcriptional co‐activator and co‐repressor complexes possessing histone acetyltransferase and deacetylase activities, respectively. Here, we report that TAL1 is subject to acetylation in vivo and can be acetylated by p300 and the p300/CBP‐associated factor P/CAF in vitro . P/CAF‐mediated acetylation, which mapped to a lysine‐rich motif in the loop region, increased TAL1 binding to DNA while selectively inhibiting its interaction with the transcriptional co‐repressor mSin3A. Furthermore, P/CAF protein, TAL1–P/CAF interaction and TAL1 acetylation increased significantly in murine erythroleukemia cells induced to differentiate in culture, while enforced expression of an acetylation‐defective P/CAF mutant inhibited endogenous TAL1 acetylation, TAL1 DNA‐binding activity, TAL1‐directed transcription and terminal differentiation of these cells. These results reveal a novel mechanism by which TAL1 activity is regulated and implicate acetylation of this transcription factor in promotion of erythroid differentiation.