ArticleProceedings of the National Academy of Sciences of the United States of America2013
Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation.
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 92 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Genetic alterations of histone lysine methyltransferases and their significance in breast cancer.Oncotarget · 2015Pooled it
- ERα/SIRT1 signaling mediates the metabolic regulatory benefits of pterostilbene.The Journal of biological chemistry · 2026Article
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- KDM5A methylation modulates its genomic demethylase and transcriptional actions.The Journal of biological chemistry · 2026Article
- Histone methyltransferase SET-18/SMYD2-mediated activation of NADase TIR-1d/SARM1 increases mtROS to promote aging.iScience · 2026Article
- Canonical and Non-Canonical Functions of Histone H3K4 Methylation Modifiers in Cancer.Cancer science · 2025Review
- Immunohistochemical Profiling of Histone Modification Biomarkers Identifies Subtype-Specific Epigenetic Signatures and Potential Drug Targets in Breast Cancer.International journal of molecular sciences · 2025Article
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- SMYD2 Promotes Calcium Oxalate-Induced Glycolysis in Renal Tubular Epithelial Cells via PTEN Methylation.Biomedicines · 2024Article
- A new method for network bioinformatics identifies novel drug targets for mucinous ovarian carcinoma.NAR genomics and bioinformatics · 2024Article
- Methylation of the chromatin modifier KMT2D by SMYD2 contributes to therapeutic response in hormone-dependent breast cancer.Cell reports · 2024Article
- Lysine methyltransferase SMYD2 enhances androgen receptor signaling to modulate CRPC cell resistance to enzalutamide.Oncogene · 2024Article
- The role of epigenetics in women's reproductive health: the impact of environmental factors.Frontiers in endocrinology · 2024Review
- Computational approach for assessing the involvement of SMYD2 protein in human cancers using TCGA data.Journal, genetic engineering & biotechnology · 2023Article
- SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin.Cellular and molecular life sciences : CMLS · 2023Article
- Nuclear PRMT5 is a biomarker of sensitivity to tamoxifen in ERαEMBO molecular medicine · 2023Article
- SMYD2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Intimal Hyperplasia via Interaction with Myocardin.Research square · 2023Article
- Zinc finger myeloid Nervy DEAF-1 type (ZMYND) domain containing proteins exert molecular interactions to implicate in carcinogenesis.Discover oncology · 2022Review
- STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells.Journal of molecular neuroscience : MN · 2022Article
- Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer.World journal of gastroenterology · 2022Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogen receptor alpha (ERα) is a ligand-activated transcription factor. Upon estrogen stimulation, ERα recruits a number of coregulators, including both coactivators and corepressors, to the estrogen response elements, modulating gene activation or repression. Most coregulator complexes contain histone-modifying enzymes to control ERα target gene expression in an epigenetic manner. In addition to histones, these epigenetic modifiers can modify nonhistone proteins including ERα, thereby constituting another layer of transcriptional regulation. Here we show that SET and MYND domain containing 2 (SMYD2), a histone H3K4 and H3K36 methyltransferase, directly methylates ERα protein at lysine 266 (K266) both in vitro and in cells. In breast cancer MCF7 cells, SMYD2 attenuates the chromatin recruitment of ERα to prevent ERα target gene activation under an estrogen-depleted condition. Importantly, the SMYD2-mediated repression of ERα target gene expression is mediated by the methylation of ERα at K266 in the nucleus, but not the methylation of histone H3K4. Upon estrogen stimulation, ERα-K266 methylation is diminished, thereby enabling p300/cAMP response element-binding protein-binding protein to acetylate ERα at K266, which is known to promote ERα transactivation activity. Our study identifies a previously undescribed inhibitory methylation event on ERα. Our data suggest that the dynamic cross-talk between SMYD2-mediated ERα protein methylation and p300/cAMP response element-binding protein-binding protein-dependent ERα acetylation plays an important role in fine-tuning the functions of ERα at chromatin and the estrogen-induced gene expression profiles.
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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.