Hdl Handle:
http://hdl.handle.net/10675.2/747
Title:
Modulation of Dnmt3b function in vitro by interactions with Dnmt3L, Dnmt3a and Dnmt3b splice variants
Authors:
Van Emburgh, Beth O.; Robertson, Keith D.
Abstract:
DNA methylation, an essential regulator of transcription and chromatin structure, is established and maintained by the coordinated action of three DNA methyltransferases: DNMT1, DNMT3A and DNMT3B, and the inactive accessory factor DNMT3L. Disruptions in DNMT3B function are linked to carcinogenesis and genetic disease. DNMT3B is also highly alternatively spliced in a tissue- and disease-specific manner. The impact of intra-DNMT3 interactions and alternative splicing on the function of DNMT3 family members remains unclear. In the present work, we focused on DNMT3B. Using a panel of in vitro assays, we examined the consequences of DNMT3B splicing and mutations on its ability to bind DNA, interact with itself and other DNMT3's, and methylate DNA. Our results show that, while the C-terminal catalytic domain is critical for most DNMT3B functions, parts of the N-terminal region, including the PWWP domain, are also important. Alternative splicing and domain deletions also influence DNMT3Bâ s cellular localization. Furthermore, our data reveal the existence of extensive DNMT3B self-interactions that differentially impact on its activity. Finally, we show that catalytically inactive isoforms of DNMT3B are capable of modulating the activity of DNMT3Aâ DNMT3L complexes. Our studies therefore suggest that seemingly â inactiveâ DNMT3B isoforms may influence genomic methylation patterns in vivo.
Citation:
Nucleic Acids Res. 2011 Jul 4; 39(12):4984-5002
Issue Date:
4-Jul-2011
URI:
http://hdl.handle.net/10675.2/747
DOI:
10.1093/nar/gkr116
PubMed ID:
21378119
PubMed Central ID:
PMC3130282
Type:
Article
ISSN:
1362-4962
Appears in Collections:
Department of Biochemistry and Molecular Biology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorVan Emburgh, Beth O.en_US
dc.contributor.authorRobertson, Keith D.en_US
dc.date.accessioned2012-10-26T20:27:55Z-
dc.date.available2012-10-26T20:27:55Z-
dc.date.issued2011-07-4en_US
dc.identifier.citationNucleic Acids Res. 2011 Jul 4; 39(12):4984-5002en_US
dc.identifier.issn1362-4962en_US
dc.identifier.pmid21378119en_US
dc.identifier.doi10.1093/nar/gkr116en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/747-
dc.description.abstractDNA methylation, an essential regulator of transcription and chromatin structure, is established and maintained by the coordinated action of three DNA methyltransferases: DNMT1, DNMT3A and DNMT3B, and the inactive accessory factor DNMT3L. Disruptions in DNMT3B function are linked to carcinogenesis and genetic disease. DNMT3B is also highly alternatively spliced in a tissue- and disease-specific manner. The impact of intra-DNMT3 interactions and alternative splicing on the function of DNMT3 family members remains unclear. In the present work, we focused on DNMT3B. Using a panel of in vitro assays, we examined the consequences of DNMT3B splicing and mutations on its ability to bind DNA, interact with itself and other DNMT3's, and methylate DNA. Our results show that, while the C-terminal catalytic domain is critical for most DNMT3B functions, parts of the N-terminal region, including the PWWP domain, are also important. Alternative splicing and domain deletions also influence DNMT3Bâ s cellular localization. Furthermore, our data reveal the existence of extensive DNMT3B self-interactions that differentially impact on its activity. Finally, we show that catalytically inactive isoforms of DNMT3B are capable of modulating the activity of DNMT3Aâ DNMT3L complexes. Our studies therefore suggest that seemingly â inactiveâ DNMT3B isoforms may influence genomic methylation patterns in vivo.en_US
dc.rights© The Author(s) 2011. Published by Oxford University Press.en_US
dc.subjectGene Regulation, Chromatin and Epigeneticsen_US
dc.titleModulation of Dnmt3b function in vitro by interactions with Dnmt3L, Dnmt3a and Dnmt3b splice variantsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3130282en_US
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biology-
dc.contributor.corporatenameGHSU Cancer Center-

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