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PMID: 2583102 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Suppression of MHC class I gene expression by N-myc through enhancer inactivation.

The EMBO journal ·Vol. 8 ·No. 11 ·1989-11-00 ·Pages 3351-5

Lenardo M, Rustgi AK, Schievella AR, Bernards R

Abstract

Amplification of the N-myc oncogene in human neuroblastoma is associated with increased metastatic ability. We previously found that over-expression of N-myc in rat neuroblastoma tumor cells causes a dramatic reduction in the expression of MHC class I mRNA. We show here that two distinct elements in the promoter render the MHC class I genes susceptible to N-myc-mediated suppression, one of which was identified as the MHC class I gene enhancer. Our data indicate that elevated N-myc expression is associated with reduced binding of a transcription factor that activates this enhancer. As a result, the activity of the MHC class I gene enhancer is greatly diminished. Elevated expression of the N-myc oncogene in human neuroblastomas and murine pre-B lymphoid lines also correlated with reduced factor binding to the MHC class I gene enhancer. Thus, an important effect of N-myc may be to impair the function of certain cellular enhancers by altering the levels of their cognate binding proteins.

MeSH Terms
Animals Electrophoresis, Polyacrylamide Gel Enhancer Elements, Genetic Gene Expression Genes, MHC Class I Humans Mutation Neuroblastoma Oncogenes Promoter Regions, Genetic Suppression, Genetic Transcription Factors/metabolism Transfection Tumor Cells, Cultured
Chemicals
Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lenardo M
Whitehead Institute for Biomedical Research, Cambridge MA 02142.
Rustgi A K
Schievella A R
Bernards R
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1989-11-00
Pages
3351-5
Language
English
Region
England
NLM ID
8208664
PMCID
PMC401475
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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