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P/CAF-mediated acetylation regulates the function of the basic helix-loop-helix transcription factor TAL1/SCL
1Departments of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
The EMBO Journal
|December 16, 2000
Summary
Acetylation regulates the transcription factor TAL1, enhancing its DNA binding and promoting erythroid differentiation. This finding reveals a new mechanism controlling TAL1 activity in blood development.
Area of Science:
- Molecular Biology
- Cell Biology
- Hematopoiesis
Background:
- The transcription factor TAL1 is crucial for hematopoietic and vascular development.
- TAL1 misexpression is linked to T-cell acute lymphoblastic leukemia.
- TAL1 interacts with co-activator and co-repressor complexes.
Purpose of the Study:
- To investigate the role of TAL1 acetylation in its regulatory functions.
- To identify the enzymes responsible for TAL1 acetylation.
- To elucidate the impact of acetylation on TAL1 activity and cellular differentiation.
Main Methods:
- In vivo and in vitro acetylation assays using p300 and P/CAF.
- Analysis of TAL1-DNA and TAL1-protein interactions.
- Functional studies in murine erythroleukemia cells using wild-type and mutant P/CAF.
Main Results:
- TAL1 is acetylated in vivo by p300 and P/CAF.
- P/CAF-mediated acetylation enhances TAL1 DNA binding and inhibits interaction with mSin3A.
- Acetylation of TAL1 is increased during erythroid differentiation and is critical for this process.
Conclusions:
- TAL1 activity is regulated by acetylation.
- Acetylation of TAL1 by P/CAF promotes erythroid differentiation.
- This study uncovers a novel mechanism of TAL1 regulation via post-translational modification.