Nature Immunology
5, 1069 - 1077 (2004)
Published online: 12 September 2004; | doi:10.1038/ni1119
Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcriptionHolly Maier1, Rachel Ostraat1, Hua Gao2, Scott Fields1, Susan A Shinton3, Kay L Medina4, Tomokatsu Ikawa5, Cornelis Murre5, Harinder Singh4, Richard R Hardy3
& James Hagman1, 21
Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, and University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. 2
Program in Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. 3
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 4
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA. 5
Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093, USA.
Correspondence should be addressed to James Hagman hagmanj@njc.org
Cd79a (called mb-1 here) encodes the Ig- 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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