Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription

Holly Maier, Rachel Ostraat, Hua Gao, Scott Fields, Susan A. Shinton, Kay L. Medina, Tomokatsu Ikawa, Cornelis Murre, Harinder Singh, Richard R. Hardy, James Hagman

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Cd79a (called mb-1 here) encodes the Ig-α signaling component of the B cell receptor. The early B cell-specific mb-1 promoter was hypermethylated at CpG dinucleotides in hematopoietic stem cells but became progressively unmethylated as B cell development proceeded. The transcription factor Pax5 activated endogenous mb-1 transcription in a plasmacytoma cell line, but could not when the promoter was methylated. In this context, early B cell factor (EBF), a transcription factor required for B lymphopoiesis, potentiated activation of mb-1 by Pax5. EBF and the basic helix-loop-helix transcription factor E47 each contributed to epigenetic modifications of the mb-1 promoter, including CpG demethylation and nucleosomal remodeling. EBF function was enhanced by interaction with the transcription factor Runx1. These data suggest a molecular basis for the hierarchical dependence of Pax5 function on EBF and E2A in B lymphocyte development.

Original languageEnglish (US)
Pages (from-to)1069-1077
Number of pages9
JournalNature immunology
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Maier, H., Ostraat, R., Gao, H., Fields, S., Shinton, S. A., Medina, K. L., Ikawa, T., Murre, C., Singh, H., Hardy, R. R., & Hagman, J. (2004). Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nature immunology, 5(10), 1069-1077. https://doi.org/10.1038/ni1119