Glucocorticoid receptor-dependent gene regulatory networks

Phillip Phuc Le, Joshua R. Friedman, Jonathan Schug, John E. Brestelli, J. Brandon Parker, Irina M. Bochkis, Klaus H. Kaestner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)159-170
Number of pages12
JournalPLoS genetics
Volume1
Issue number2
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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