DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity

Sebastiaan H Meijsing; Miles A Pufall; Alex Y So; Darren L Bates; Lin Chen; Keith R Yamamoto

doi:10.1126/science.1164265

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DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity

Journal article

Peer reviewed

DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity

Sebastiaan H Meijsing, Miles A Pufall, Alex Y So, Darren L Bates, Lin Chen and Keith R Yamamoto

Science (American Association for the Advancement of Science), Vol.324(5925), pp.407-410

04/17/2009

DOI: 10.1126/science.1164265

PMCID: PMC2777810

PMID: 19372434

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Abstract

Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.

Details

Title: Subtitle: DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity
Creators: Sebastiaan H Meijsing - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
Miles A Pufall - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
Alex Y So - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
Darren L Bates - Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
Lin Chen - Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
Keith R Yamamoto - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.324(5925), pp.407-410
DOI: 10.1126/science.1164265
PMID: 19372434
PMCID: PMC2777810
NLM abbreviation: Science
ISSN: 0036-8075
eISSN: 1095-9203
Publisher: American Association for the Advancement of Science (AAAS)
Language: English
Date published: 04/17/2009
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9984024559602771

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