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PMID: 2162764 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nuclear factor I acts as a transcription factor on the MMTV promoter but competes with steroid hormone receptors for DNA binding.

The EMBO journal ·Vol. 9 ·No. 7 ·1990-07-00 ·Pages 2233-9

Brüggemeier U, Rogge L, Winnacker EL, Beato M

Abstract

Several steroid hormones induce transcription of the mouse mammary tumor virus (MMTV) promoter, through an interaction of their respective receptors with the hormone responsive elements (HREs) in the long terminal repeat (LTR) region. The molecular mechanism underlying transcriptional activation is not known, but binding of nuclear factor I (NFI) to a site adjacent to the HRE appears to be required for efficient transcription of the MMTV promoter. In JEG-3 choriocarcinoma cells the MMTV promoter is transcribed inefficiently, even after transfection of the receptor cDNA and treatment with glucocorticoids or progestins. These cells contain low levels of NFI as cotransfection of NFI cDNA enhances MMTV transcription and this effect is inhibited by mutation of the NFI binding site. In DNA binding experiments with purified NFI from pig liver, the glucocorticoid and progesterone receptors do not co-operate but rather compete with NFI for binding to their respective sites on the LTR. Similar results are obtained with a functional recombinant NFI synthesized in vitro. Competition for DNA binding is probably due to steric hindrance as the DNase I footprints of the hormone receptors and NFI do overlap. These results suggest that, though NFI acts as a transcription factor on the MMTV promoter, transcriptional activation does not take place through a direct facilitation of DNA binding of NFI by steroid hormone receptors.

MeSH Terms
Animals Base Sequence Binding Sites Binding, Competitive CCAAT-Enhancer-Binding Proteins Cell Line DNA, Circular/genetics DNA, Superhelical/genetics DNA-Binding Proteins/metabolism Female Liver/metabolism Mammary Tumor Virus, Mouse/genetics Molecular Sequence Data NFI Transcription Factors Nuclear Proteins Oligonucleotide Probes Plasmids Promoter Regions, Genetic Rabbits Rats Receptors, Glucocorticoid/metabolism Receptors, Progesterone/metabolism Transcription Factors/metabolism Transcription, Genetic Transfection Uterus/metabolism Y-Box-Binding Protein 1
Chemicals
CCAAT-Enhancer-Binding Proteins DNA, Circular DNA, Superhelical DNA-Binding Proteins NFI Transcription Factors Nuclear Proteins Oligonucleotide Probes Receptors, Glucocorticoid Receptors, Progesterone Transcription Factors Y-Box-Binding Protein 1 YBX1 protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Brüggemeier U
Institut für Molekularbiologie und Tumorforschung, Philipps Universität, Marburg, FRG.
Rogge L
Winnacker E L
Beato M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-07-00
Pages
2233-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC551947
Subset
IM
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