Saksela, Kalle and Baltimore, David (1993) Negative regulation of immunoglobulin kappa light-chain gene transcription by a short sequence homologous to the murine B1 repetitive element. Molecular and Cellular Biology, 13 (6). pp. 3698-3705. ISSN 0270-7306. http://resolver.caltech.edu/CaltechAUTHORS:SAKmcb93
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B-cell-specific expression of the immunoglobulin kappa light-chain (Ig kappa) gene is in part accomplished by negative regulatory influences. Here we describe a new negatively acting element (termed kappa NE) immediately upstream of the NF-kappa B-binding site in the Ig kappa intronic enhancer. The 27-bp kappa NE sequence is conserved in the corresponding positions in the rabbit and human Ig kappa genes, and the human kappa NE homolog was shown to have a similar negative regulatory activity. Data base searches using the mouse kappa NE sequence revealed a striking homology to murine B1 repetitive sequences. A sequence homologous to kappa NE and B1 was also noted in a previously identified silencer element in the murine T-cell receptor alpha locus. The homologous T-cell receptor alpha locus sequence, but notably not a corresponding 27-bp B1 consensus sequence, showed a negative regulatory potential similar to that of kappa NE. The negative effect of kappa NE by itself was not cell type specific but became so when paired with its 5'-flanking sequence in the Ig kappa enhancer. A short (30-bp) fragment upstream of kappa NE (termed kappa BS) was found to be necessary and sufficient for abolishing the negative effect of kappa NE in B cells. Point mutations in a T-rich motif within the kappa BS sequence allowed the transcriptional repression by kappa NE to be evident in B cells as well as other cells. As suggested by this cell-independent negative activity, proteins binding to the mouse and human kappa NE sequences were identified in all cell types tested.
|Additional Information:||Copyright © 1993 by the American Society for Microbiology. Received 21 December 1992; Returned for modification 22 February 1993; Accepted 25 March 1993. We thank Chris Roman for valuable comments on the manuscript and Patricia Cortes for help and suggestions in the band shift experiments. K.S. was supported by an EMBO postdoctoral fellowship. This work was supported by NIH grant GM39458-04 to D.B.|
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|Deposited On:||04 Feb 2008|
|Last Modified:||26 Dec 2012 09:49|
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