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PMID: 16110340 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Glucocorticoid receptor-dependent gene regulatory networks.

PLoS genetics ·Vol. 1 ·No. 2 ·2005-08-00 ·Pages e16

Phuc Le P, Friedman JR, Schug J, Brestelli JE, Parker JB, Bochkis IM, Kaestner KH

Abstract

While the molecular mechanisms of glucocorticoid regulation of transcription have been studied in detail, the global networks regulated by the glucocorticoid receptor (GR) remain unknown. To address this question, we performed an orthogonal analysis to identify direct targets of the GR. First, we analyzed the expression profile of mouse livers in the presence or absence of exogenous glucocorticoid, resulting in over 1,300 differentially expressed genes. We then executed genome-wide location analysis on chromatin from the same livers, identifying more than 300 promoters that are bound by the GR. Intersecting the two lists yielded 53 genes whose expression is functionally dependent upon the ligand-bound GR. Further network and sequence analysis of the functional targets enabled us to suggest interactions between the GR and other transcription factors at specific target genes. Together, our results further our understanding of the GR and its targets, and provide the basis for more targeted glucocorticoid therapies.

MeSH Terms
Animals Chromatin Gene Expression Profiling Gene Expression Regulation Genome Liver/metabolism Male Mice Mice, Inbred Strains Promoter Regions, Genetic Receptors, Glucocorticoid/physiology Regulatory Sequences, Nucleic Acid
Chemicals
Chromatin Receptors, Glucocorticoid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Phuc Le Phillip
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Friedman Joshua R
Schug Jonathan
Brestelli John E
Parker J Brandon
Bochkis Irina M
Kaestner Klaus H
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7390
DOI
10.1371/journal.pgen.0010016
Published
2005-08-00
Epub
2005-00-05
Pages
e16
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1186734
Subset
IM
Grants
NIDDK NIH HHS · U01 DK056947 · United States
NIDDK NIH HHS · DK49210 · United States
NIDDK NIH HHS · DK56947 · United States
NIDDK NIH HHS · R24 DK056947 · United States
NIDDK NIH HHS · P01 DK049210 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.0010016 PMC Full Text
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