TY - CHAP
T1 - Mechanisms of DNA methylation, methyl-CpG recognition, and demethylation in mammals
AU - Cheng, Xiaodong
AU - Hashimoto, Hideharu
AU - Horton, John R.
AU - Zhang, Xing
N1 - Funding Information:
We thank most warmly our colleagues and coworkers whose hard work was responsible for much of the DNA and histone methylation work cited in this review. Work in the authors’ laboratory is supported in part by grants (US National Institutes of Health GM049245, GM068680, and DK082678) and the Georgia Research Alliance. This chapter is an updated version of our previous articles “Mammalian DNA methyltransferases: A structural perspective” (originally published in Structure 16 , March 2008, pp. 341–350; with permission from Elsevier) and “UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications” (originally published in Epigenetics 4 , pp. 8–14; January 2009, with permission from Landes Bioscience).
PY - 2011
Y1 - 2011
N2 - This chapter summarizes the recent structural and biochemical advances in the study of mammalian DNA MTases and their associated protein factor(s), and touches on the functional links between histone modification and that of DNA. The mammalian cells can be very broadly divided into three categories-intrinsic promoter strength and availability of core transcription machinery, the actions of promoter- or regulon-specific transcription factors (positive and negative), and the control of DNA accessibility by altering chromatin structure. Modifications to histones and postreplicational modification of DNA are the focus of recent extensive studies. In mammals and other vertebrates, DNA methylation occurs at the C5 position of cytosine (5mC), mostly within CpG dinucleotides, with the Dnmt enzymes using a conserved mechanism. This mechanism involves MTase binding to the DNA, eversion of the target nucleotide so that it projects out of the double helix ("base flipping"), covalent attack of a conserved Cys nucleophile on cytosine C6, transfer of the methyl group from S-adenosylL-methionine (AdoMet) to the activated cytosine C5, and the various release steps. This methylation, together with histone modifications, plays an important role in modulating chromatin structure, thus controlling gene expression and many other chromatin-dependent processes.
AB - This chapter summarizes the recent structural and biochemical advances in the study of mammalian DNA MTases and their associated protein factor(s), and touches on the functional links between histone modification and that of DNA. The mammalian cells can be very broadly divided into three categories-intrinsic promoter strength and availability of core transcription machinery, the actions of promoter- or regulon-specific transcription factors (positive and negative), and the control of DNA accessibility by altering chromatin structure. Modifications to histones and postreplicational modification of DNA are the focus of recent extensive studies. In mammals and other vertebrates, DNA methylation occurs at the C5 position of cytosine (5mC), mostly within CpG dinucleotides, with the Dnmt enzymes using a conserved mechanism. This mechanism involves MTase binding to the DNA, eversion of the target nucleotide so that it projects out of the double helix ("base flipping"), covalent attack of a conserved Cys nucleophile on cytosine C6, transfer of the methyl group from S-adenosylL-methionine (AdoMet) to the activated cytosine C5, and the various release steps. This methylation, together with histone modifications, plays an important role in modulating chromatin structure, thus controlling gene expression and many other chromatin-dependent processes.
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U2 - 10.1016/B978-0-12-375709-8.00002-2
DO - 10.1016/B978-0-12-375709-8.00002-2
M3 - Chapter
AN - SCOPUS:84055197603
SN - 9780123757098
SP - 9
EP - 24
BT - Handbook of Epigenetics
PB - Elsevier Inc.
ER -