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

Holly Maier; Rachel Ostraat; Hua Gao; Scott Fields; Susan A. Shinton; Kay L. Medina; Tomokatsu Ikawa; Cornelis Murre; Harinder Singh; Richard R. Hardy; James Hagman

doi:10.1038/ni1119

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

Holly Maier, Rachel Ostraat, Hua Gao, Scott Fields, Susan A. Shinton, Kay L. Medina, Tomokatsu Ikawa, Cornelis Murre, Harinder Singh, Richard R. Hardy, James Hagman

Immunology

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140 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1069-1077
Number of pages	9
Journal	Nature immunology
Volume	5
Issue number	10
DOIs	https://doi.org/10.1038/ni1119
State	Published - Oct 2004

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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@article{6e354edd781c4b978338a78204bc7419,

title = "Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription",

abstract = "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.",

author = "Holly Maier and Rachel Ostraat and Hua Gao and Scott Fields and Shinton, {Susan A.} and Medina, {Kay L.} and Tomokatsu Ikawa and Cornelis Murre and Harinder Singh and Hardy, {Richard R.} and James Hagman",

note = "Funding Information: 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.",

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T1 - Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription

AU - Maier, Holly

AU - Ostraat, Rachel

AU - Gao, Hua

AU - Fields, Scott

AU - Shinton, Susan A.

AU - Medina, Kay L.

AU - Ikawa, Tomokatsu

AU - Murre, Cornelis

AU - Singh, Harinder

AU - Hardy, Richard R.

AU - Hagman, James

N1 - Funding Information: 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.

PY - 2004/10

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N2 - 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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Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription

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