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Nucleic Acids Research, 1994, Vol. 22, No. 9 1576-1582
© 1994


MOLECULAR BIOLOGY

Activation of the immunoglobulin {chi}3' enhancer in pre-B cells correlates with the suppression of a nuclear factor binding to a sequence flanking the active core

Kerstin B. Meyer1,* and John Ireland

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 {chi} intron and the {chi}3' enhancer are required for high levels of immunoglobulin {chi} gene expression. The activity of both enhancer elements can be induced by LPS in pre-B cells. While the LPS induction of the {chi} intron enhancer is mediated by NF-{chi}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 {chi}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 {chi} gene transcription.


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