Cited by 283Estrogen and related hormone effectsGenomics and Chromatin DynamicsStress Responses and Cortisol

Glucocorticoid Receptor Binding to a Specific DNA Sequence Is Required for Hormone-Dependent Repression of Pro-Opiomelanocortin Gene Transcription

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Drouin, Jacques, Trifiro, Mark A., Plante, Richard K., Nemer, Mona, Eriksson, Per, Wrange, Örjan·1989·Molecular and Cellular Biology

Abstract

Glucocorticoids rapidly and specifically inhibit transcription of the pro-opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences.

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Crossref · 10.1128/mcb.9.12.5305-5314.1989

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Authors
Drouin, J., Trifiro, M. A., Plante, R. K., Nemer, M., Eriksson, P., & Wrange, Ö.
Affiliations
  • Montreal Clinical Research Institute (CA)
  • Karolinska Institutet (SE)
  • Department of Molecular Genetics, Karolinska Institutet
Venue
Molecular and Cellular Biology
Published
1989-12
Volume
9
Issue
12
Pages
5305-5314
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2161628453
Cited by
283
References
71
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 2
FWCI
12.99
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
glucocorticoid receptor, transcriptional repression, glucocorticoid response element, anterior pituitary, AtT-20 cells, sequence divergence
MeSH terms
Animals, Base Sequence, DNA, Genes, Molecular Sequence Data, Nucleotide Mapping, Pituitary Gland, Anterior, Plasmids, Pro-Opiomelanocortin, Protein Binding, Receptors, Glucocorticoid, Suppression, Genetic, Transcription, Genetic, Restriction Mapping, Rats

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