Differential recruitment of glucocorticoid receptor phospho-isoforms to glucocorticoid-induced genes
Open accessAbstract
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.
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Different GR phosphoisoforms selectively occupy promoters of different GR target genes.
“different GR phosphoisoforms have been reported to selectively occupy promoters of different GR target genes”
From Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor (2011) · cites this paper as [65]
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- Authors
- Blind, R. D., & Garabedian, M. J.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- Corresponding author
- Garabedian, Michael J.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 109
- Issue
- 1-2
- Pages
- 150-157
- ISSN
- 0960-0760 (ISSN-L)
- PMC
- PMC2699583
- OpenAlex
- W1990118125
- Cited by
- 120
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 7
- FWCI
- 8.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058024, R01DK054836, DK54836)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- glucocorticoid receptor, receptor phosphorylation, activation functions, glucocorticoid response element, tyrosine aminotransferase, GILZ, transcriptional activation, rat hepatoma cells, U2OS cells
- MeSH terms
- Animals, Base Sequence, Binding Sites, Dexamethasone, DNA, Humans, Phosphorylation, Receptors, Glucocorticoid, RNA, Messenger, Transcription Factors, Tyrosine Transaminase, Arylsulfotransferase, Transcriptional Activation, DNA Primers, Protein Isoforms, Cell Line, Tumor, Rats
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