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

EMBO J. 2000 Dec 15;19(24):6792-803. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism*
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Binding Sites
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation
  • Conserved Sequence
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Helix-Loop-Helix Motifs
  • Histone Acetyltransferases
  • Humans
  • Leukemia, Erythroblastic, Acute
  • Lysine
  • Mice
  • Protein Biosynthesis
  • Proto-Oncogene Proteins*
  • Recombinant Proteins / metabolism
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • p300-CBP Transcription Factors


  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse
  • Transcription Factors
  • TAL1 protein, human
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Lysine