Regulation of E2A activities by histone acetyltransferases in B lymphocyte development.
Genetic studies have demonstrated that the basic helix-loop-helix protein E2A is an essential transcription factor in B lymphocyte lineage commitment and differentiation. However, the mechanism underlying E2A-mediated transcription regulation is not fully understood. Here, we investigated the physical and genetic interactions between E2A and co-activators histone acetyltransferases (HATs) in B ... cells. Gel filtration analysis of human pre-B cell nuclear extract showed that E2A co-elutes with the HATs p300, CBP, and PCAF. A co-immunoprecipitation assay further demonstrated that a fraction of endogenous E2A proteins is associated with each of the three HATs. We show that these HATs acetylate E2A in vitro, enhance E2A-mediated transcription activity, and promote nuclear retention of E2A proteins. A catalytic mutation of p300 completely abrogates the ability of p300 to acetylate E2A and to promote E2A nuclear retention in 293T cells. A breeding test between E2A heterozygous mice and p300 heterozygous mice demonstrated that these two genes interact for proper B cell development. Collectively, these results suggest that E2A and HATs collaboratively regulate B cell development.
Mesh Terms:
Acetyltransferases, Age Factors, Animals, Animals, Newborn, B-Lymphocytes, Basic Helix-Loop-Helix Transcription Factors, Blotting, Western, Cell Nucleus, Cell Separation, Cells, Cultured, Chromatography, Gel, DNA-Binding Proteins, E1A-Associated p300 Protein, Flow Cytometry, Gene Expression Regulation, Developmental, Genes, Reporter, Hela Cells, Heterozygote, Histone Acetyltransferases, Humans, Luciferases, Mice, Microscopy, Fluorescence, Mutation, Nuclear Proteins, Precipitin Tests, Protein Binding, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
Acetyltransferases, Age Factors, Animals, Animals, Newborn, B-Lymphocytes, Basic Helix-Loop-Helix Transcription Factors, Blotting, Western, Cell Nucleus, Cell Separation, Cells, Cultured, Chromatography, Gel, DNA-Binding Proteins, E1A-Associated p300 Protein, Flow Cytometry, Gene Expression Regulation, Developmental, Genes, Reporter, Hela Cells, Heterozygote, Histone Acetyltransferases, Humans, Luciferases, Mice, Microscopy, Fluorescence, Mutation, Nuclear Proteins, Precipitin Tests, Protein Binding, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
J. Biol. Chem.
Date: Jan. 24, 2003
PubMed ID: 12435739
View in: Pubmed Google Scholar
Download Curated Data For This Publication
4405
Switch View:
- Interactions 13