NDLI: Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development.

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Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Timblin, Greg A. Schlissel, Mark S.
Description	Author Affiliation: Timblin GA ( Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.)
Abstract	The temporal control of RAG (Rag) expression in developing lymphocytes prevents DNA breaks during periods of proliferation that could threaten genomic integrity. In developing B cells, the IL-7R and precursor B cell Ag receptor (pre-BCR) synergize to induce proliferation and the repression of Rag at the protein and mRNA levels for a brief period following successful Ig H chain gene rearrangement. Whereas the mechanism of RAG2 protein downregulation is well defined, little is known about the pathways and transcription factors that mediate transcriptional repression of Rag. Using Abelson murine leukemia virus-transformed B cells to model this stage of development, we identified early B cell factor 1 (Ebf1) as a strong repressor of Rag transcription. Short hairpin RNA-mediated knockdown of either Ebf1 or its downstream target c-Myb was sufficient to induce Rag transcription in these highly proliferative cells. Ebf1 and c-Myb antagonize Rag transcription by negatively regulating the binding of Foxo1 to the Rag locus. Ebf1 accomplishes this through both direct negative regulation of Foxo1 expression and direct positive regulation of Gfi1b expression. Ebf1 expression is driven by the IL-7R downstream effector Stat5, providing a link between the negative regulation of Rag transcription by IL-7 and a novel repressive pathway involving Ebf1 and c-Myb.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1301675
Journal	The Journal of Immunology
Issue Number	9
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	B-lymphocytes Metabolism Homeodomain Proteins Genetics Proto-oncogene Proteins C-myb Stat5 Transcription Factor Trans-activators Animals Cell Differentiation Immunology Cell Proliferation Cells, Cultured Dna-binding Proteins Forkhead Transcription Factors Biosynthesis Interleukin-7 Mice Mice, Inbred C57bl Proto-oncogene Proteins Rna Interference Rna, Small Interfering Repressor Proteins Signal Transduction Transcription, Genetic Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Ebf1 and c-Myb repress Rag transcription downstream of Stat5 during early B cell development

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Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development.

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Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development.