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Differential recruitment of glucocorticoid receptor phospho-isoforms to glucocorticoid-induced genes.

Blind RD, Garabedian MJ
J Steroid Biochem Mol Biol. 2008 109 (1-2): 150-7

PMID: 18304804 · PMCID: PMC2699583 · DOI:10.1016/j.jsbmb.2008.01.002

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.

MeSH Terms (17)

Animals Arylsulfotransferase Base Sequence Binding Sites Cell Line, Tumor Dexamethasone DNA DNA Primers Humans Phosphorylation Protein Isoforms Rats Receptors, Glucocorticoid RNA, Messenger Transcriptional Activation Transcription Factors Tyrosine Transaminase

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