Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription.
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.
Maier
Holly
H
Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Ostraat
Rachel
R
Gao
Hua
H
Fields
Scott
S
Shinton
Susan A
SA
Medina
Kay L
KL
Ikawa
Tomokatsu
T
Murre
Cornelis
C
Singh
Harinder
H
Hardy
Richard R
RR
Hagman
James
J
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001402:B-Lymphocytes / Q000502:physiology; D051925:CD79 Antigens; D002843:Chromatin / Q000737:chemistry; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000502:physiology*; D003640:Dealkylation; D051379:Mice; D008810:Mice, Inbred C57BL; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D002843:Chromatin; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; C493726:Runx1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors