Enzymology of Mammalian DNA Methyltransferases.
DNA methylation
DNA methyltransferase
DNMT1
DNMT3A
DNMT3B
Enzyme mechanism
Enzyme regulation
Enzyme specifcity
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2022
2022
Historique:
entrez:
9
11
2022
pubmed:
10
11
2022
medline:
15
11
2022
Statut:
ppublish
Résumé
DNA methylation is a hot topic in basic and biomedical research. Despite tremendous progress in understanding the structures and biochemical properties of the mammalian DNA methyltransferases (DNMTs), principles of their targeting and regulation in cells have only begun to be uncovered. In mammals, DNA methylation is introduced by the DNMT1, DNMT3A, and DNMT3B enzymes, which are all large multi-domain proteins containing a catalytic C-terminal domain and a complex N-terminal part with diverse targeting and regulatory functions. The sub-nuclear localization of DNMTs plays an important role in their biological function: DNMT1 is localized to replicating DNA and heterochromatin via interactions with PCNA and UHRF1 and direct binding to the heterochromatic histone modifications H3K9me3 and H4K20me3. DNMT3 enzymes bind to heterochromatin via protein multimerization and are targeted to chromatin by their ADD, PWWP, and UDR domains, binding to unmodified H3K4, H3K36me2/3, and H2AK119ub1, respectively. In recent years, a novel regulatory principle has been discovered in DNMTs, as structural and functional data demonstrated that the catalytic activities of DNMT enzymes are under a tight allosteric control by their different N-terminal domains with autoinhibitory functions. This mechanism provides numerous possibilities for the precise regulation of the methyltransferases via controlling the binding and release of the autoinhibitory domains by protein partners, chromatin interactions, non-coding RNAs, or posttranslational modifications of the DNMTs. In this chapter, we summarize key enzymatic properties of DNMTs, viz. their specificity and processivity, and afterwards focus on the regulation of their activity and targeting via allosteric processes, protein interactions, and posttranslational modifications.
Identifiants
pubmed: 36350507
doi: 10.1007/978-3-031-11454-0_4
doi:
Substances chimiques
Heterochromatin
0
DNA Methyltransferase 3A
EC 2.1.1.37
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
DNA Modification Methylases
EC 2.1.1.-
Chromatin
0
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-110Informations de copyright
© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.
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