Regulation of E2A activities by histone acetyltransferases in B lymphocyte development

J Biol Chem. 2003 Jan 24;278(4):2370-6. doi: 10.1074/jbc.M211464200. Epub 2002 Nov 14.

Abstract

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.

Publication types

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

MeSH terms

  • Acetyltransferases / metabolism*
  • Age Factors
  • Animals
  • Animals, Newborn
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / physiology
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Western
  • Cell Nucleus / metabolism
  • Cell Separation
  • Cells, Cultured
  • Chromatography, Gel
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics*
  • E1A-Associated p300 Protein
  • Flow Cytometry
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • HeLa Cells
  • Heterozygote
  • Histone Acetyltransferases
  • Humans
  • Luciferases / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Mutation
  • Nuclear Proteins / metabolism
  • Precipitin Tests
  • Protein Binding
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Trans-Activators / metabolism
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • TCF3 protein, human
  • Trans-Activators
  • Transcription Factors
  • Luciferases
  • Acetyltransferases
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse
  • Histone Acetyltransferases