P/CAF-mediated acetylation regulates the function of the basic helix-loop-helix transcription factor TAL1/SCL.
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.
Huang
S
S
Departments of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Qiu
Y
Y
Shi
Y
Y
Xu
Z
Z
Brandt
S J
SJ
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs; D051548:Histone Acetyltransferases; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008239:Lysine; D051379:Mice; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D008239:Lysine; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human