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- Title
Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription.
- Authors
Maier, Holly; Ostraat, Rachel; Hua Gao; Fields, Scott; Shinton, Susan A.; Medina, Kay L.; Ikawa, Tomokatsu; Murre, Cornelis; Singh, Harinder; Hardy, Richard R.; Hagman, James
- Abstract
Cd79a (called mb-1 here) encodes the Ig-α signaling component of the B cell receptor. The early B cell-specific mb-i 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-i 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.
- Subjects
LYMPHOCYTES; B cells; PROTEINS; TRANSCRIPTION factors; HEMATOPOIETIC stem cells; BONE marrow cells
- Publication
Nature Immunology, 2004, Vol 5, Issue 10, p1069
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni1119