Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 109, Issue 1-2, Pages 150-157Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2008.01.002
Keywords
glucocorticoid receptor; phosphorylation; gene expression; chromatin immunoprecipitation
Funding
- NIDDK NIH HHS [DK54836, R01 DK058024-04, R01 DK058024, R01 DK054836] Funding Source: Medline
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The human glucocorticoid receptor (GR) is phosphorylated on its N-terminus at three major sites (S203, S211 and S226) within activation function 1 (AF1). Although GR has been shown to assemble at glucocorticoid responsive elements (GREs) in the presence of hormone, the timing and specificity of GR phospho-isoform recruitment to receptor target genes has not been established. Using chromatin immunoprecipitation (ChIP) and GR phosphorylation site-specific antibodies, we examined GR phospho-isoform recruitment to several glucocorticoid-induced genes including tyrosine aminotransferase (tat) and sulfonyltransferase-1A1 (sult) in rat hepatoma cells, and the glucocorticoid-induced leucine zipper (gilz) gene in human U2OS cells. GR P-S211 and GR P-S226 isoforms were efficiently recruited to the tat, sult and gilz GREs in a hormone-dependent manner. In contrast, the GR P-S203 isoform. displayed no significant recruitment to any GREs of the genes analyzed, consistent with its lack of nuclear accumulation. Interestingly, the kinetics of GR P-S211 and GR P-S226 recruitment differed among genes. Our findings indicate that GR phospho-isoforms selectively occupy GR target genes, and suggests gene specific requirements for GR phosphorylation in receptor-dependent transcriptional activation. (C) 2008 Elsevier Ltd. All rights reserved.
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