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.
Bradney
Curtis
C
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Hjelmeland
Mark
M
Komatsu
Yasuhiko
Y
Yoshida
Minoru
M
Yao
Tso-Pang
TP
Zhuang
Yuan
Y
D000123:Acetyltransferases / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D050881:E1A-Associated p300 Protein; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006367:HeLa Cells; D006579:Heterozygote; D051548:Histone Acetyltransferases; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D000123:Acetyltransferases; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases; D008156:Luciferases; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C407909:TCF3 protein, human; C494361:Ep300 protein, mouse