Epigenetic regulations of DNA and histone methylation and deMethylation: Structures and Mechanisms

DNA 和组蛋白甲基化和去甲基化的表观遗传调控：结构和机制

• 批准号: 10794474
• 负责人: Xiaodong Cheng
• 金额: $ 25万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10794474
• 关键词: Biochemical; Brain; Cell Differentiation process; Cytosine; DNA; DNA Methylation; DNA Methylation Regulation; DNA Modification Methylases; DNA Modification Process; Development; Dioxygenases; Enzymes; Epigenetic Process; Event; Fetus; Gene Expression; Generations; Genome; Genomics; Germ Lines; Maintenance; Mammalian Cell; Mammals; Methylation; Modification; Molecular; Positioning Attribute; Proteins; Reaction; Role; Series; Structure; T cell differentiation; demethylation; epigenetic memory; epigenetic regulation; histone methylation; oxidation; programs; transcription factor; young adult

Summary/Abstract The control of gene expression in mammals relies in part on modifications to cytosine residues in DNA, which exist in at least five forms: cytosine (C), 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5- formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methyltransferases methylate cytosine at the 5- position, generating 5mC in the genome. Ten-eleven translocation (Tet) dioxygenases convert 5mC to 5hmC, 5fC, and 5caC in three consecutive oxidation reactions. These modifications are dynamically regulated during development and cell differentiation. To understand the function of these modifications and the regulatory mechanisms that control the levels and genomic distribution of the five forms of the cytosine, we propose to study the enzymes/proteins that generate, read, and remove these DNA modifications as well as associated histone methylation.

摘要/摘要 哺乳动物基因表达的控制在一定程度上依赖于DNA中胞嘧啶残基的修饰，这是 至少以五种形式存在：胞嘧啶(C)、5-甲基胞嘧啶(5mC)、5-羟甲基胞嘧啶(5HmC)、5-甲基胞嘧啶(5mC)、 甲酰胞嘧啶(5fC)和5-羧基胞嘧啶(5caC)。DNA甲基转移酶5-甲基化胞嘧啶 定位，在基因组中产生5mC。10-11易位(Tet)双加氧酶将5mC转化为5hmC， 5fC和5caC连续三次氧化反应。这些修改在以下过程中动态调整 发育和细胞分化。要了解这些修改的功能和监管 控制五种形式胞嘧啶水平和基因组分布的机制，我们建议 研究产生、读取和移除这些DNA修饰的酶/蛋白质以及相关的 组蛋白甲基化。

项目成果

Enzymatic characterization of mRNA cap adenosine-N6 methyltransferase PCIF1 activity on uncapped RNAs.

• DOI: 10.1016/j.jbc.2022.101751
• 发表时间: 2022-04
• 期刊: The Journal of biological chemistry
• 作者: Yu D;Dai N;Wolf EJ;Corrêa IR Jr;Zhou J;Wu T;Blumenthal RM;Zhang X;Cheng X
• 通讯作者: Cheng X

Structural basis for human ZBTB7A action at the fetal globin promoter.

人类 ZBTB7A 对胎儿珠蛋白启动子作用的结构基础

• DOI: 10.1016/j.celrep.2021.109759
• 发表时间: 2021-09-28
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Yang Y;Ren R;Ly LC;Horton JR;Li F;Quinlan KGR;Crossley M;Shi Y;Cheng X
• 通讯作者: Cheng X

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences.

• DOI: 10.1093/nar/gkaa446
• 发表时间: 2020-10-09
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Woodcock CB;Horton JR;Zhang X;Blumenthal RM;Cheng X
• 通讯作者: Cheng X

Mediating and maintaining methylation while minimizing mutation: Recent advances on mammalian DNA methyltransferases.

• DOI: 10.1016/j.sbi.2022.102433
• 发表时间: 2022-08
• 期刊: CURRENT OPINION IN STRUCTURAL BIOLOGY
• 影响因子: 6.8
• 作者: Cheng, Xiaodong;Blumenthal, Robert M.
• 通讯作者: Blumenthal, Robert M.

Systematic Design of Adenosine Analogs as Inhibitors of a Clostridioides difficile-Specific DNA Adenine Methyltransferase Required for Normal Sporulation and Persistence.

• DOI: 10.1021/acs.jmedchem.2c01789
• 发表时间: 2023-01-12
• 期刊: JOURNAL OF MEDICINAL CHEMISTRY
• 影响因子: 7.3
• 作者: Zhou, Jujun;Horton, John R.;Menna, Martina;Fiorentino, Francesco;Ren, Ren;Yu, Dan;Hajian, Taraneh;Vedadi, Masoud;Mazzoccanti, Giulia;Ciogli, Alessia;Weinhold, Elmar;Hueben, Michael;Blumenthal, Robert M.;Zhang, Xing;Mai, Antonello;Rotili, Dante;Cheng, Xiaodong
• 通讯作者: Cheng, Xiaodong