Regulation of E2A activities by histone acetyltransferases in B lymphocyte development.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bradney, C; Hjelmeland, M; Komatsu, Y; Yoshida, M; Yao, T-P; Zhuang, Y

Published Date

  • January 24, 2003

Published In

Volume / Issue

  • 278 / 4

Start / End Page

  • 2370 - 2376

PubMed ID

  • 12435739

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M211464200


  • eng

Conference Location

  • United States