Downstream activation of a TATA-less promoter by Oct-2, Bob1, and NF-kappaB directs expression of the homing receptor BLR1 to mature B cells.
The chemokine receptor, BLR1, is a major regulator of the microenvironmental homing of B cells in lymphoid organs. In vitro studies identify three essential elements of the TATA-less blr1 core promoter that confer cell type- and differentiation-specific expression in the B cells of both humans and mice, a functional promoter region (-36 with respect to the transcription start site), a NF-kappaB motif (+44), and a noncanonical octamer motif (+157). The importance of these sites was confirmed by in vivo studies in gene-targeted mice deficient of either Oct-2, Bob1, or both NF-kappaB subunits p50 and p52. In all of these animals, the expression of BLR1 was reduced or absent. In mice deficient only of p52/NF-kappaB, BLR1 expression was unaffected. Thus our data demonstrate that BLR1 is a target gene for Oct-2, Bob1, and members of the NF-kappaB/Rel family and provides a link to the impaired B cell functions in mice deficient for these factors.
Wolf
I
I
Department of Tumorgenetics and Immunogenetics, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13122, Berlin-Buch, Germany.
Pevzner
V
V
Kaiser
E
E
Bernhardt
G
G
Claudio
E
E
Siebenlist
U
U
Förster
R
R
Lipp
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050813:Octamer Transcription Factor-2; D011401:Promoter Regions, Genetic; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*; D016385:TATA Box; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C095085:CXCR5 protein, human; C513179:CXCR5 protein, mouse; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050813:Octamer Transcription Factor-2; C091546:POU2AF1 protein, human; C058435:POU2F2 protein, human; C490424:Pou2af1 protein, mouse; C489206:Pou2f2 protein, mouse; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015534:Trans-Activators; D014157:Transcription Factors; D019204:GTP-Binding Proteins