Publication Date:
2009-04-18
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777810/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meijsing, Sebastiaan H -- Pufall, Miles A -- So, Alex Y -- Bates, Darren L -- Chen, Lin -- Yamamoto, Keith R -- GM08537/GM/NIGMS NIH HHS/ -- R01 CA020535/CA/NCI NIH HHS/ -- R01 CA020535-31/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):407-10. doi: 10.1126/science.1164265.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372434" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Base Sequence
;
Binding Sites
;
Cell Line, Tumor
;
Crystallography, X-Ray
;
DNA/*chemistry/*metabolism
;
Humans
;
Ligands
;
Models, Molecular
;
Mutation
;
Protein Conformation
;
Protein Isoforms/chemistry/metabolism
;
Protein Multimerization
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Rats
;
Receptors, Glucocorticoid/chemistry/genetics/*metabolism
;
Transcriptional Activation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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