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Structural Basis of DNMT1 and DNMT3A-Mediated DNA Methylation

by Wendan Ren 1,†, Linfeng Gao 2,† and Jikui Song 1,2,*
1
Department of Biochemistry, University of California, Riverside, CA 92521, USA
2
Environmental Toxicology Program, University of California, Riverside, CA 92521, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2018, 9(12), 620; https://doi.org/10.3390/genes9120620
Received: 7 November 2018 / Revised: 30 November 2018 / Accepted: 4 December 2018 / Published: 11 December 2018
(This article belongs to the Special Issue Role of DNA Methyltransferases in the Epigenome)
DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. The establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B, which are responsible for installing DNA methylation patterns during gametogenesis and early embryogenesis, and DNMT1, which is essential for propagating DNA methylation patterns during replication. Both groups of DNMTs are multi-domain proteins, containing a large N-terminal regulatory region in addition to the C-terminal methyltransferase domain. Recent structure-function investigations of the individual domains or large fragments of DNMT1 and DNMT3A have revealed the molecular basis for their substrate recognition and specificity, intramolecular domain-domain interactions, as well as their crosstalk with other epigenetic mechanisms. These studies highlight a multifaceted regulation for both DNMT1 and DNMT3A/3B, which is essential for the precise establishment and maintenance of lineage-specific DNA methylation patterns in cells. This review summarizes current understanding of the structure and mechanism of DNMT1 and DNMT3A-mediated DNA methylation, with emphasis on the functional cooperation between the methyltransferase and regulatory domains. View Full-Text
Keywords: DNMT1; DNMT3A; DNA methyltransferase; maintenance DNA methylation; de novo DNA methylation; allosteric regulation; autoinhibition DNMT1; DNMT3A; DNA methyltransferase; maintenance DNA methylation; de novo DNA methylation; allosteric regulation; autoinhibition
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Ren, W.; Gao, L.; Song, J. Structural Basis of DNMT1 and DNMT3A-Mediated DNA Methylation. Genes 2018, 9, 620.

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