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PMID: 2120037 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A novel upstream element compensates for an ineffectual octamer motif in an immunoglobulin V kappa promoter.

The EMBO journal ·Vol. 9 ·No. 10 ·1990-10-00 ·Pages 3109-17

Atchison ML, Delmas V, Perry RP

Abstract

The octamer (or dc/cd) motif is considered to be a critical component of all immunoglobulin (Ig) promoters. Although the sequence of this motif is highly conserved among most Ig promoters, there are some notable examples in which efficiently expressed Ig genes contain divergent octamers with base substitutions that are demonstrably deleterious when tested with heterologous proximal promoter elements. To elucidate the mechanisms that enable these naturally occurring Ig genes to cope with divergent octamers, we analyzed two such promoters with regard to their ability to interact with relevant transcription factors. We found that the divergent octamer in the kappa O germline promoter strongly binds both Oct-1 and Oct-2 factors, presumably because of compensatory contributions by flanking DNA sequences. A more surprising result was obtained with the V kappa 19 promoter. In this case, the divergent octamer is a very weak Oct factor binding site and, without help from another upstream element, is inadequate for efficient promoter function. This additional element, termed kappa Y because of its high pyrimidine content (CTTCCTTA), serves as a binding site for a novel lymphoid-specific factor. When the divergent V kappa 19 octamer was converted to a strong Oct factor binding site by a single point mutation, the need for kappa Y was obviated. Interestingly, VH promoters that contain the same divergent octamer also contain an upstream element that is very similar to kappa Y.

MeSH Terms
Animals B-Lymphocytes/immunology Base Sequence Cell Line DNA-Binding Proteins/metabolism Genes, Immunoglobulin Humans Immunoglobulin Variable Region/genetics Immunoglobulin kappa-Chains/genetics Mice Molecular Sequence Data Multigene Family Mutagenesis, Site-Directed Nuclear Proteins/metabolism Octamer Transcription Factor-2 Oligonucleotide Probes Plasmacytoma Plasmids Promoter Regions, Genetic Restriction Mapping Sequence Homology, Nucleic Acid Transcription Factors Transfection
Chemicals
DNA-Binding Proteins Immunoglobulin Variable Region Immunoglobulin kappa-Chains Nuclear Proteins Octamer Transcription Factor-2 Oligonucleotide Probes POU2F2 protein, human Pou2f2 protein, mouse Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Atchison M L
Fox Chase Cancer Center, Philadelphia, PA 19111.
Delmas V
Perry R P
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45 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-10-00
Pages
3109-17
Language
English
Region
England
NLM ID
8208664
PMCID
PMC552038
Subset
IM
Grants
NIAID NIH HHS · AI-17330 · United States
NCI NIH HHS · CA-06927 · United States
NCRR NIH HHS · RR-05539 · United States
External Links
PubMed source PMC Full Text View journal details
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