{"title":"A Chemogenetic System for Spatiotemporal Perturbation of Cellular Methylation Potential","authors":"Shusuke Ogihara, Yuuta Fujikawa, Ayaka Fujieda, Shio Horiuchi, Rika Kasai, Fumika Hatano, Taiki Ogura, Ryosuke Kojima, Isshin Shiiba, Hideshi Inoue, Yoshio Hayashi, Yasuteru Urano, Toru Komatsu","doi":"10.1021/acschembio.6c00548","DOIUrl":null,"url":null,"abstract":"<p>We developed a genetically encoded system to perturb the methylation potential of living cells by exploiting the metabolic consumption of <em>S</em>-adenosylmethionine (SAM) through a plant methyltransferase, eugenol <em>O</em>-methyltransferase 1 (EOMT1). This system enables control of intracellular SAM levels with spatio- and temporal precision, regulated by the expression of EOMT1 and the timing of eugenol addition. EOMT1 expression allowed concentration-dependent reduction of SAM levels within 30 min. The system revealed distinct histone marks such as H3K4me3, H3K9me3, and H3K27me3, which responded differentially to SAM perturbation, revealing variable sensitivity between histone methyltransferases and demethylases. In addition, the spatially restricted expression of EOMT1 enabled the metabolic link of SAM between multiple organelles.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 10","pages":"2675–2682"},"PeriodicalIF":3.6000,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Biology","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acschembio.6c00548","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/9/28 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
We developed a genetically encoded system to perturb the methylation potential of living cells by exploiting the metabolic consumption of S-adenosylmethionine (SAM) through a plant methyltransferase, eugenol O-methyltransferase 1 (EOMT1). This system enables control of intracellular SAM levels with spatio- and temporal precision, regulated by the expression of EOMT1 and the timing of eugenol addition. EOMT1 expression allowed concentration-dependent reduction of SAM levels within 30 min. The system revealed distinct histone marks such as H3K4me3, H3K9me3, and H3K27me3, which responded differentially to SAM perturbation, revealing variable sensitivity between histone methyltransferases and demethylases. In addition, the spatially restricted expression of EOMT1 enabled the metabolic link of SAM between multiple organelles.
期刊介绍：
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.
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