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Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression

Libermann, Towia Aron and Lenardo, Michael and Baltimore, David (1990) Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression. Molecular and Cellular Biology, 10 (6). pp. 3155-3162. ISSN 0270-7306. http://resolver.caltech.edu/CaltechAUTHORS:20120509-104303031

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Abstract

To determine whether enhancer elements in addition to the highly conserved octamer (OCTA)-nucleotide motif are important for lymphoid-specific expression of the immunoglobulin heavy-chain (IgH) gene, we have investigated the effect of mutating the binding site for a putative additional lymphoid-specific transcription factor, designated NF-microB, in the murine IgH enhancer. We demonstrate that the NF-microB-binding site plays a critical role in the IgH enhancer, because mutation of the microB DNA motif decreased transcriptional activity of the IgH enhancer in cells of the B-cell lineage but not in nonlymphoid cells. This effect was comparable to or even stronger than the effect of a mutation in the OCTA site. Moreover, combined mutation of both microB and OCTA sites further reduced enhancer activity in lymphoid cells. Interestingly, alteration of either the microB or E3 site in a 70-base-pair fragment of the IgH enhancer that lacks the binding site for OCTA abolished enhancer activity in lymphoid cells completely. Nevertheless, a multimer of the microB motif alone showed no enhancer activity. DNase footprinting analysis corroborated the functional data showing that a lymphoid-specific protein binds to the microB DNA motif. Our results suggest that the microB element is a new crucial element important for lymphoid-specific expression of the IgH gene but that interaction with another enhancer element is essential for its activity.


Item Type:Article
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http://mcb.asm.org/content/10/6/3155PublisherUNSPECIFIED
Additional Information:© 1990 American Society for Microbiology. Received 13 December 1989; Accepted 8 March 1990. We thank Barbara Nelsen, Tom Kadesch, and Ranjan Sen for communicating their results to us prior to publication. We thank Jacqueline Pierce and Stephen Smale for helpful discussions. This work was supported by a fellowship from the Leukemia Society of America to T.A.L., a National Cancer Institute clinical investigator award to M.L., and Public Health Service grant GM 39458 to D.B. from the National Institutes of Health.
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Funding AgencyGrant Number
Leukemia Society of AmericaUNSPECIFIED
National Cancer InstituteUNSPECIFIED
U. S. Public Health Service (USPHS)GM 39458
Record Number:CaltechAUTHORS:20120509-104303031
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120509-104303031
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:31374
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 May 2012 22:22
Last Modified:26 Dec 2012 15:10

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