Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter

Mikael Sigvardsson, Dawn R. Clark, Daniel Fitzsimmons, Michelle Doyle, Peter Åkerblad, Thomas Breslin, Sven Bilke, Ronggui Li, Carmen Yeamans, Gongyi Zhang, James Hagman

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Previous studies have suggested that the early-B-cell-specific mb.1 (Igα) promoter is regulated by EBF and Pax-5. Here, we used in vivo footprinting assays to detect occupation of binding sites in endogenous mb-1 promoters at various stages of B-cell differentiation. In addition to EBF and Pax-5 binding sites, we detected occupancy of a consensus binding site for E2A proteins (E box) in pre-B cells. EBF and E box sites are crucial for promoter function in transfected pre-B cells, and EBF and E2A proteins synergistically activated the promoter in transfected HeLa cells. Other data suggest that EBF and E box sites are less important for promoter function at later stages of differentiation, whereas binding sites for Pax-5 (and its Ets ternary complex partners) are required for promoter function in all mb-1-expressing cells. Using DNA microarrays, we found that expression of endogenous mb-1 transcripts correlates most closely with EBF expression and negatively with Id1, an inhibitor of E2A protein function, further linking regulation of the mb-1 gene with EBF and E2A. Together, our studies demonstrate the complexity of factors regulating tissue-specific transcription and support the concept that EBF, E2A, and Pax-5 cooperate to activate target genes in early B-cell development.

Original languageEnglish (US)
Pages (from-to)8539-8551
Number of pages13
JournalMolecular and cellular biology
Volume22
Issue number24
DOIs
StatePublished - Dec 2002

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