Epigenetic regulation of histone methyltransferase SUV39H1 on the expression of recombinant protein in CHO cells

IF 3.9 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Applied Microbiology and Biotechnology Pub Date : 2025-05-10 DOI:10.1007/s00253-025-13509-y

Lu-Lu Yang, Miao Zhang, Jia-Liang Guo, Ming-Ming Han, Le-Le Qiu, Li-Jie Gao, Liu-Su Cui, Xiao-Yin Wang, Tian-Yun Wang, Yan-Long Jia

{"title":"Epigenetic regulation of histone methyltransferase SUV39H1 on the expression of recombinant protein in CHO cells","authors":"Lu-Lu Yang, Miao Zhang, Jia-Liang Guo, Ming-Ming Han, Le-Le Qiu, Li-Jie Gao, Liu-Su Cui, Xiao-Yin Wang, Tian-Yun Wang, Yan-Long Jia","doi":"10.1007/s00253-025-13509-y","DOIUrl":null,"url":null,"abstract":"<div><h3>Abstract</h3><p>Histone methylation–mediated epigenetic modification significantly influences gene transcription and expression regulation. This study examined the effects of histone 3 lysine 9 trimethylation (H3K9me3) methyltransferase SUV39H1 and its specific inhibitor chaetocin on recombinant protein expression in Chinese hamster ovary (CHO) cells. Results indicated that stable SUV39H1-knockdown CHO cells exhibited reduced H3K9me3 levels while showing increased expression of recombinant adalimumab (rADM) and human serum albumin (rHSA) by approximately 45% and 136%, respectively. Furthermore, treatment with 20 nM chaetocin, a SUV39H1-specific inhibitor, enhanced expression of enhanced green fluorescent protein (EGFP), rADM, and rHSA in CHO cells. These findings demonstrate that both stable SUV39H1 knockdown and pharmacological inhibition through chaetocin effectively reduce H3K9me3 modification levels in CHO cells while significantly boosting recombinant protein production. The results strongly suggest SUV39H1’s critical regulatory role in recombinant protein expression within CHO cell systems. This research establishes a methodological foundation for developing engineered cell lines and optimizing high-efficiency CHO expression systems through cell engineering approaches.</p><h3>Key points</h3><p><i>•SUV39H1 knockdown boosted recombinant protein expression and decreased H3 K9 me3 levels.</i></p><p><i>•Treatment with the SUV39H1-specific inhibitor chaetocin (20 nM) enhanced recombinant protein expression.</i></p><p><i>•It provides a basis for developing efficient epigenetically regulated CHO expression systems.</i></p></div>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00253-025-13509-y.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Applied Microbiology and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://link.springer.com/article/10.1007/s00253-025-13509-y","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Histone methylation–mediated epigenetic modification significantly influences gene transcription and expression regulation. This study examined the effects of histone 3 lysine 9 trimethylation (H3K9me3) methyltransferase SUV39H1 and its specific inhibitor chaetocin on recombinant protein expression in Chinese hamster ovary (CHO) cells. Results indicated that stable SUV39H1-knockdown CHO cells exhibited reduced H3K9me3 levels while showing increased expression of recombinant adalimumab (rADM) and human serum albumin (rHSA) by approximately 45% and 136%, respectively. Furthermore, treatment with 20 nM chaetocin, a SUV39H1-specific inhibitor, enhanced expression of enhanced green fluorescent protein (EGFP), rADM, and rHSA in CHO cells. These findings demonstrate that both stable SUV39H1 knockdown and pharmacological inhibition through chaetocin effectively reduce H3K9me3 modification levels in CHO cells while significantly boosting recombinant protein production. The results strongly suggest SUV39H1’s critical regulatory role in recombinant protein expression within CHO cell systems. This research establishes a methodological foundation for developing engineered cell lines and optimizing high-efficiency CHO expression systems through cell engineering approaches.

Key points

•SUV39H1 knockdown boosted recombinant protein expression and decreased H3 K9 me3 levels.

•Treatment with the SUV39H1-specific inhibitor chaetocin (20 nM) enhanced recombinant protein expression.

•It provides a basis for developing efficient epigenetically regulated CHO expression systems.

查看原文本刊更多论文

组蛋白甲基转移酶SUV39H1对CHO细胞重组蛋白表达的表观遗传调控

摘要：甲基化介导的表观遗传修饰显著影响基因转录和表达调控。本研究探讨了组蛋白3 - lysine 9三甲基化（H3K9me3）甲基转移酶SUV39H1及其特异性抑制剂chaecin对中国仓鼠卵巢（CHO）细胞重组蛋白表达的影响。结果表明，稳定敲除suv39h1的CHO细胞显示H3K9me3水平降低，重组阿达木单抗（rADM）和人血清白蛋白（rHSA）的表达分别增加约45%和136%。此外，20 nM chaeoxytocin （suv39h1特异性抑制剂）可增强CHO细胞中增强绿色荧光蛋白（EGFP）、rADM和rHSA的表达。这些结果表明，SUV39H1的稳定敲除和chaeoxin的药理抑制都能有效降低CHO细胞中H3K9me3修饰水平，同时显著促进重组蛋白的产生。结果强烈提示SUV39H1在CHO细胞系统中重组蛋白表达的关键调控作用。本研究为通过细胞工程方法开发工程细胞系和优化高效CHO表达系统奠定了方法学基础。•敲低SUV39H1增强重组蛋白表达，降低H3 K9 me3水平。•suv39h1特异性抑制剂缩霉素（20 nM）增强了重组蛋白的表达。•它为开发高效的表观遗传调控CHO表达系统提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Applied Microbiology and Biotechnology 工程技术-生物工程与应用微生物

CiteScore

10.00

自引率

4.00%

发文量

535

审稿时长

2 months

期刊介绍： Applied Microbiology and Biotechnology focusses on prokaryotic or eukaryotic cells, relevant enzymes and proteins; applied genetics and molecular biotechnology; genomics and proteomics; applied microbial and cell physiology; environmental biotechnology; process and products and more. The journal welcomes full-length papers and mini-reviews of new and emerging products, processes and technologies.