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.
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The authors thank P. Kincade (Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma) for providing the SB199 hybridoma; M. Reth (Max-Planck Institute, Tubingen, Germany) for providing the 558LμM cell line; M. Busslinger (Institute for Molecular Pathology, Vienna, Austria) for providing the Pax5−/− mice; and S. McNeff for assistance with illustrations. Supported by National Institutes of Health (T32 AI07405 to H.M.; R01 AI26782 and R01 AI40946 to R.R.H.; and P01 AI22295, R01 AI054661 and R01 AI056322 to J.H.), the Irvington Institute for Immunological Research (K.L.M.) and the Milheim Foundation.
The authors declare no competing financial interests.
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Maier, H., Ostraat, R., Gao, H. et al. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol 5, 1069–1077 (2004). https://doi.org/10.1038/ni1119
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