ArticleProceedings of the National Academy of Sciences of the United States of America2012
G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of glucocorticoid receptor target genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 140 citations in OpenAlex.
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- Histone methyltransferase G9a crosstalks with H3K36 histone methyltransferases NSD3 and SETD2 to mediate gene activation.Frontiers in cell and developmental biology · 2026Article
- G9a controls plasma cell differentiation through FOXO1 and ETS1 binding site regulatory networks.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Emerging Trends and Hot Spots in Epigenetic Modifications in Neurology: A Bibliometric Analysis.Molecular neurobiology · 2025Review
- Molecular mechanisms altering cell identity in cancer.Oncogene · 2025Review
- Setdb2 Regulates Inflammatory Trigger-Induced Trained Immunity of Macrophages Through Two Different Epigenetic Mechanisms.Research square · 2025Article
- The histone H3K9 methyltransferase G9a regulates tendon formation during development.Scientific reports · 2024Article
- Discovery of the First-in-Class G9a/GLP PROTAC Degrader.Journal of medicinal chemistry · 2024Article
- Discovery of the First-in-class G9a/GLP PROTAC Degrader.bioRxiv : the preprint server for biology · 2024Article
- Loss of G9a does not phenocopy the requirement for Prdm12 in the development of the nociceptive neuron lineage.Neural development · 2024Article
- Histone methylation: at the crossroad between circadian rhythms in transcription and metabolism.Frontiers in genetics · 2024Review
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?Endocrine reviews · 2023Review
- Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators.Pharmacology & therapeutics · 2023Review
- PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer.Life science alliance · 2023Article
- CMOT: Cross-Modality Optimal Transport for multimodal inference.Genome biology · 2023Article
- Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice.Nature communications · 2023Article
- G9a Modulates Lipid Metabolism in CD4 T Cells to Regulate Intestinal Inflammation.Gastroenterology · 2023Article
- Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Histone H3 lysine-9 methyltransferase G9a/EHMT2/KMT1C is a key corepressor of gene expression. However, activation of a limited number of genes by G9a (independent of its catalytic activity) has also been observed, although the precise molecular mechanisms are unknown. By using RNAi in combination with gene expression microarray analysis, we found that G9a functions as a positive and a negative transcriptional coregulator for discrete subsets of genes that are regulated by the hormone-activated Glucocorticoid Receptor (GR). G9a was recruited to GR-binding sites (but not to the gene body) of its target genes and interacted with GR, suggesting recruitment of G9a by GR. In contrast to its corepressor function, positive regulation of gene expression by G9a involved G9a-mediated enhanced recruitment of coactivators CARM1 and p300 to GR target genes. Further supporting a role for G9a as a molecular scaffold for its coactivator function, the G9a-specific methyltransferase inhibitor UNC0646 did not affect G9a coactivator function but selectively decreased G9a corepressor function for endogenous target genes. Overall, G9a functioned as a coactivator for hormone-activated genes and as a corepressor in support of hormone-induced gene repression, suggesting that the positive or negative actions of G9a are determined by the gene-specific regulatory environment and chromatin architecture. These findings indicate distinct mechanisms of G9a coactivator vs. corepressor functions in transcriptional regulation and provide insight into the molecular mechanisms of G9a coactivator function. Our results also suggest a physiological role of G9a in fine tuning the set of genes that respond to glucocorticoids.
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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.