title: Oligomerization and binding of the Dnmt3a DNA methyltransferase to parallel DNA molecules: heterochromatic localization and role of Dnmt3L.
abstract: Structural studies showed that Dnmt3a has two interfaces for protein-protein interaction in the heterotetrameric Dnmt3a/3L C-terminal domain complex: the RD interface (mediating the Dnmt3a-3a contact) and the FF interface (mediating the Dnmt3a-3L contact). Here, we demonstrate that Dnmt3a-C forms dimers via the FF interface as well, which further oligomerize via their RD interfaces. Each RD interface of the Dnmt3a-C oligomer creates an independent DNA binding site, which allows for binding of separate DNA molecules oriented in parallel. Because Dnmt3L does not have an RD interface, it prevents Dnmt3a oligomerization and binding of more than one DNA molecule. Both interfaces of Dnmt3a are necessary for the heterochromatic localization of the enzyme in cells. Overexpression of Dnmt3L in cells leads to the release of Dnmt3a from heterochromatic regions, which may increase its activity for methylation of euchromatic targets like the differentially methylated regions involved in imprinting.
authors.affiliation: Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Renata Z
authors.initials: RZ
authors.lastname: Jurkowska
authors.forename: Arumugam
authors.initials: A
authors.lastname: Rajavelu
authors.forename: Nils
authors.initials: N
authors.lastname: Anspach
authors.forename: Claus
authors.initials: C
authors.lastname: Urbanke
authors.forename: Gytis
authors.initials: G
authors.lastname: Jankevicius
authors.forename: Sergey
authors.initials: S
authors.lastname: Ragozin
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nellen
authors.forename: Albert
authors.initials: A
authors.lastname: Jeltsch
mesh_terms: D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology; D000090205:DNA Methyltransferase 3A; D018392:Genomic Imprinting / Q000502:physiology; D006570:Heterochromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D055503:Protein Multimerization / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: C000715535:Dnmt3a protein, mouse; D006570:Heterochromatin; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A