Role of lysine methylation of NF-?B in differential gene regulation

Lu T.; Yang M.; Huang D.-B.Wei H.Ozer G.H.Ghosh G.Stark G.R.

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Role of lysine methylation of NF-?B in differential gene regulation

机译：Role of lysine methylation of NF-?B in differential gene regulation

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Lysine methylation of the p65 subunit of nuclear factor ?B (NF-?B) on K218 and K221 together or K37 alone strongly enhances gene expression in response to cytokines. We analyzed the effects of Kto-Q mutations in the REL homology domain of p65 on the response to IL-1? in 293 cells with low levels of p65. The K218/221Q mutation greatly reduced the expression of 39 of 82 genes, whereas the K37Q mutation reduced the expression of 23 different genes. Enhanced expression of the lysine demethylase FBXL11, which catalyzes the demethylation of K218 and K221 specifically, inhibited the expression of most of the genes that were inhibited by the DKQ mutation. CHIP-Seq analysis showed that the K218/221Q mutation greatly reduces the affinity of p65 for many promoters and that the K37Q mutation does not. Structural modeling showed that the newly introduced methyl groups of K218 and K221 interact directly with DNA to increase the affinity of p65 for specific ?B sites. Thus, the K218/221Q and K37Q mutations have dramatically different effects because methylations of these residues affect different genes by distinct mechanisms.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第33期|13510-13515|共6页
作者
Lu T.; Yang M.; Huang D.-B.Wei H.Ozer G.H.Ghosh G.Stark G.R.;
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作者单位

Department of Molecular Genetics, Cleveland Clinic, Cleveland, OH 44195, United States;

Department of Chemistry and Biochemistry, University of California at San Diego, San Diego, CA 92093, United States;

Department of Pharmacology and Toxicology, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United StatesDepartment of Biomedical Informatics, Ohio State University Medical Center, Columbus, OH 43210, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Histone modifying enzyme; Protein methylation;

Role of lysine methylation of NF-?B in differential gene regulation

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