Early B-Cell Factor, E2A, and Pax-5 Cooperate To Activate the Early B Cell-Specific mb-1Promoter

Autor: Sigvardsson, Mikael, Clark, Dawn R., Fitzsimmons, Daniel, Doyle, Michelle, Åkerblad, Peter, Breslin, Thomas, Bilke, Sven, Li, Ronggui, Yeamans, Carmen, Zhang, Gongyi, Hagman, James
Zdroj: Molecular and Cellular Biology; December 2002, Vol. 22 Issue: 24 p8539-8551, 13p
Abstrakt: ABSTRACTPrevious 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-1promoters 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-1transcripts correlates most closely with EBF expression and negatively with Id1, an inhibitor of E2A protein function, further linking regulation of the mb-1gene 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.
Databáze: Supplemental Index