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

Maier H, Ostraat R, Gao H, Fields S, Shinton SA, Medina KL, Ikawa T, Murre C, Singh H, Hardy RR, Hagman J.

Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

Cd79a (called mb-1 here) encodes the Ig-alpha 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.

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PMID: 15361869 [PubMed - indexed for MEDLINE]