Abstract
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.
Highlights
The chemokine receptor, BLR1, is a major regulator of the microenvironmental homing of B cells in lymphoid organs
BLR1 transcription initiation starts at a single site, but the promoter sequence lacks classical features like a TATA box or an initiator-like sequence
The core promoter sequence required for basic and tissue-specific expression was found to reside in a fragment encompassing a region from position Ϫ78 to ϩ215 with respect to the transcriptional start site
Summary
Vol 273, No 44, Issue of October 30, pp. 28831–28836, 1998 Printed in U.S.A. Downstream Activation of a TATA-less Promoter by Oct-2, Bob, and NF-B Directs Expression of the Homing Receptor BLR1 to Mature B Cells*. In vitro studies identify three essential elements of the TATA-less blr 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-B 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, Bob, or both NF-B subunits p50 and p52. Our data demonstrate that BLR1 is a target gene for Oct-2, Bob, and members of the NF-B/Rel family and provides a link to the impaired B cell functions in mice deficient for these factors. The observation that the B cell homing chemokine receptor, BLR1, is a target for Bob and Oct-2 links these factors to the molecule with an essential function in the immune system
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