Glucocorticoid receptor-dependent gene regulatory networks.

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.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

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

doi

10.1371/journal.pgen.0010016

keywords:

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

e16

issue

2

eissn

1553-7390

issn

1553-7404

journal_volume

1

pub_type

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