Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor

The glucocorticoid receptor (GR) associates with glucocorticoid response elements (GREs) and regulates selective gene transcription in a cell-specific manner. Native GREs are typically thought to be composite elements that recruit GR as well as other regulatory factors into functional complexes. We...

Full description

Bibliographic Details
Main Authors:	So, Alex Yick-Lun, Chaivorapol, Christina, Bolton, Eric C, Li, Hao, Yamamoto, Keith R
Format:	Online
Language:	English
Published:	Public Library of Science 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904358/

id	pubmed-1904358
recordtype	oai_dc
spelling	pubmed-19043582007-06-30 Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor So, Alex Yick-Lun Chaivorapol, Christina Bolton, Eric C Li, Hao Yamamoto, Keith R Research Article The glucocorticoid receptor (GR) associates with glucocorticoid response elements (GREs) and regulates selective gene transcription in a cell-specific manner. Native GREs are typically thought to be composite elements that recruit GR as well as other regulatory factors into functional complexes. We assessed whether GR occupancy is commonly a limiting determinant of GRE function as well as the extent to which core GR binding sequences and GRE architecture are conserved at functional loci. We surveyed 100-kb regions surrounding each of 548 known or potentially glucocorticoid-responsive genes in A549 human lung cells for GR-occupied GREs. We found that GR was bound in A549 cells predominately near genes responsive to glucocorticoids in those cells and not at genes regulated by GR in other cells. The GREs were positionally conserved at each responsive gene but across the set of responsive genes were distributed equally upstream and downstream of the transcription start sites, with 63% of them >10 kb from those sites. Strikingly, although the core GR binding sequences across the set of GREs varied extensively around a consensus, the precise sequence at an individual GRE was conserved across four mammalian species. Similarly, sequences flanking the core GR binding sites also varied among GREs but were conserved at individual GREs. We conclude that GR occupancy is a primary determinant of glucocorticoid responsiveness in A549 cells and that core GR binding sequences as well as GRE architecture likely harbor gene-specific regulatory information. Public Library of Science 2007-06 2007-06-08 /pmc/articles/PMC1904358/ /pubmed/17559307 http://dx.doi.org/10.1371/journal.pgen.0030094 Text en © 2007 So et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	So, Alex Yick-Lun Chaivorapol, Christina Bolton, Eric C Li, Hao Yamamoto, Keith R
spellingShingle	So, Alex Yick-Lun Chaivorapol, Christina Bolton, Eric C Li, Hao Yamamoto, Keith R Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
author_facet	So, Alex Yick-Lun Chaivorapol, Christina Bolton, Eric C Li, Hao Yamamoto, Keith R
author_sort	So, Alex Yick-Lun
title	Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
title_short	Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
title_full	Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
title_fullStr	Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
title_full_unstemmed	Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
title_sort	determinants of cell- and gene-specific transcriptional regulation by the glucocorticoid receptor
description	The glucocorticoid receptor (GR) associates with glucocorticoid response elements (GREs) and regulates selective gene transcription in a cell-specific manner. Native GREs are typically thought to be composite elements that recruit GR as well as other regulatory factors into functional complexes. We assessed whether GR occupancy is commonly a limiting determinant of GRE function as well as the extent to which core GR binding sequences and GRE architecture are conserved at functional loci. We surveyed 100-kb regions surrounding each of 548 known or potentially glucocorticoid-responsive genes in A549 human lung cells for GR-occupied GREs. We found that GR was bound in A549 cells predominately near genes responsive to glucocorticoids in those cells and not at genes regulated by GR in other cells. The GREs were positionally conserved at each responsive gene but across the set of responsive genes were distributed equally upstream and downstream of the transcription start sites, with 63% of them >10 kb from those sites. Strikingly, although the core GR binding sequences across the set of GREs varied extensively around a consensus, the precise sequence at an individual GRE was conserved across four mammalian species. Similarly, sequences flanking the core GR binding sites also varied among GREs but were conserved at individual GREs. We conclude that GR occupancy is a primary determinant of glucocorticoid responsiveness in A549 cells and that core GR binding sequences as well as GRE architecture likely harbor gene-specific regulatory information.
publisher	Public Library of Science
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904358/
_version_	1611397797743951872

Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor

Similar Items