P/CAF-mediated acetylation regulates the function of the basic helix-loop-helix transcription factor TAL1/SCL

• Published in: The EMBO journal Vol. 19; no. 24; pp. 6792 - 6803
• Main Authors: Huang, Suming, Qiu, Yi, Shi, Yubin, Xu, Zhixiong, Brandt, Stephen J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.12.2000; Nature Publishing Group UK; Springer Nature B.V; Oxford University Press
• Subjects: Acetylation; Acetyltransferases - metabolism; Animals; Basic Helix-Loop-Helix Transcription Factors; Binding Sites; Cell Cycle Proteins - metabolism; Cell Differentiation; co-regulator interactions; Conserved Sequence; Deoxyribonucleic acid; DNA; DNA-binding activity; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; erythroid differentiation; HeLa Cells; Helix-Loop-Helix Motifs; Histone Acetyltransferases; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Lysine; Mice; P/CAF protein; p300 protein; p300-CBP Transcription Factors; protein acetylation; Protein Biosynthesis; Proto-Oncogene Proteins; Recombinant Proteins - metabolism; SCL protein; T-Cell Acute Lymphocytic Leukemia Protein 1; TAL1; TAL1 protein; Transcription Factors - chemistry; Transcription Factors - metabolism; Transfection; Tumor Cells, Cultured; protein acetylation; co‐regulator interactions; DNA‐binding activity; TAL1; erythroid differentiation
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/19.24.6792

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.