Nucleic Acids Research, 1994, Vol. 22, No. 9 1576-1582
© 1994
MOLECULAR BIOLOGY |
Activation of the immunoglobulin
3' enhancer in pre-B cells correlates with the suppression of a nuclear factor binding to a sequence flanking the active core
The Wellcome/CRC Institute of Cancer and Developmental Biology Tennis Court Road, Cambridge CB2 1QR 1Department of Pathology, Cambridge University Cambridge, UK
*To whom correspondence should be addressed at: The Wellcome/CRC Institute of Cancer and Developmental Biology, Tennis Court Road, Cambridge CB2 1QR, UK
Received February 15, 1994. Revised April 5, 1994. Accepted April 5, 1994.
Both the
intron and the
3' enhancer are required for high levels of immunoglobulin
gene expression. The activity of both enhancer elements can be induced by LPS in pre-B cells. While the LPS induction of the
intron enhancer is mediated by NF-
B, this factor is not responsible for activation of the 3' enhancer. Dissection of the 3' enhancer has shown that in pre-B cells the activity of the
3' enhancer is repressed by a region flanking an active core element. We have now scanned this flanking region for nuclear factor binding sites and have identified sites for B-cell specific E47/E12-like proteins and two ubiquitous nuclear proteins. Furthermore, we have identified a nuclear factor in pre-B cells whose binding activity is suppressed in response to LPS. In its tissue-distribution and binding specificity this factor appears to be identical to the lymphoid specific protein LEF-1. The position of the LEF-1 binding site within the 3' enhancer and its response to LPS raise the possibility that LEF-1 may be the target for a second pathway able to mediate LPS induction of immunoglobulin
gene transcription.
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