ArticleProceedings of the National Academy of Sciences of the United States of America2013
A naturally occurring insertion of a single amino acid rewires transcriptional regulation by glucocorticoid receptor isoforms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- Glucocorticoid Insensitivity: Is It a Question of Time and Place?Biomedicines · 2025Review
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.Endocrine reviews · 2024Review
- Glucocorticoids and Their Receptor Isoforms: Roles in Female Reproduction, Pregnancy, and Foetal Development.Biology · 2023Review
- Review
- Glucocorticoid Receptor and Ovarian Cancer: From Biology to Therapeutic Intervention.Biomolecules · 2023Review
- Multimodal regulatory elements within a hormone-specific super enhancer control a heterogeneous transcriptional response.Molecular cell · 2022Article
- Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer.Cells · 2022Review
- The Non-continuum Nature of Eukaryotic Transcriptional Regulation.Advances in experimental medicine and biology · 2022Article
- Protein music of enhanced musicality by music style guided exploration of diverse amino acid properties.Heliyon · 2021Article
- Extensive epigenomic integration of the glucocorticoid response in primary human monocytes and in vitro derived macrophages.Scientific reports · 2019Article
- A General Introduction to Glucocorticoid Biology.Frontiers in immunology · 2019Review
- The first crystal structure of a DNA-free nuclear receptor DNA binding domain sheds light on DNA-driven allostery in the glucocorticoid receptor.Scientific reports · 2018Article
- The Two Faces of Adjuvant Glucocorticoid Treatment in Ovarian Cancer.Hormones & cancer · 2018Review
- A post-translational modification switch controls coactivator function of histone methyltransferases G9a and GLP.EMBO reports · 2017Article
- Nuclear Receptor Function through Genomics: Lessons from the Glucocorticoid Receptor.Trends in endocrinology and metabolism: TEM · 2017Review
- Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction.Trends in endocrinology and metabolism: TEM · 2017Review
- Comparing the rules of engagement of androgen and glucocorticoid receptors.Cellular and molecular life sciences : CMLS · 2017Review
- Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
In addition to guiding proteins to defined genomic loci, DNA can act as an allosteric ligand that influences protein structure and activity. Here we compared genome-wide binding, transcriptional regulation, and, using NMR, the conformation of two glucocorticoid receptor (GR) isoforms that differ by a single amino acid insertion in the lever arm, a domain that adopts DNA sequence-specific conformations. We show that these isoforms differentially regulate gene expression levels through two mechanisms: differential DNA binding and altered communication between GR domains. Our studies suggest a versatile role for DNA in both modulating GR activity and also in directing the use of GR isoforms. We propose that the lever arm is a "fulcrum" for bidirectional allosteric signaling, conferring conformational changes in the DNA reading head that influence DNA sequence selectivity, as well as conferring changes in the dimerization domain that connect functionally with remote regulatory surfaces, thereby influencing which genes are regulated and the magnitude of their regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.