NDLI: Dual Functions of the RFTS Domain of Dnmt1 in Replication-Coupled DNA Methylation and in Protection of the Genome from Aberrant Methylation

Content Provider	PubMed Central
Author	Garvilles, Ronald Garingalao Hasegawa, Takashi Kimura, Hironobu Sharif, Jafar Muto, Masahiro Koseki, Haruhiko Takahashi, Saori Suetake, Isao Tajima, Shoji
Editor	Feil, Robert
Copyright Year	2015
Abstract	In mammals, DNA methylation plays important roles in embryogenesis and terminal differentiation via regulation of the transcription-competent chromatin state. The methylation patterns are propagated to the next generation during replication by maintenance DNA methyltransferase, Dnmt1, in co-operation with Uhrf1. In the N-terminal regulatory region, Dnmt1 contains proliferating cell nuclear antigen (PCNA)-binding and replication foci targeting sequence (RFTS) domains, which are thought to contribute to maintenance methylation during replication. To determine the contributions of the N-terminal regulatory domains to the DNA methylation during replication, Dnmt1 lacking the RFTS and/or PCNA-binding domains was ectopically expressed in embryonic stem cells, and then the effects were analyzed. Deletion of both the PCNA-binding and RFTS domains did not significantly affect the global DNA methylation level. However, replication-dependent DNA methylation of the differentially methylated regions of three imprinted genes, Kcnq1ot1/Lit1, Peg3, and Rasgrf1, was impaired in cells expressing the Dnmt1 with not the PCNA-binding domain alone but both the PCNA-binding and RFTS domains deleted. Even in the absence of Uhrf1, which is a prerequisite factor for maintenance DNA methylation, Dnmt1 with both the domains deleted apparently maintained the global DNA methylation level, whilst the wild type and the forms containing the RFTS domain could not perform global DNA methylation under the conditions used. This apparent maintenance of the global DNA methylation level by the Dnmt1 lacking the RFTS domain was dependent on its own DNA methylation activity as well as the presence of de novo-type DNA methyltransferases. We concluded that the RFTS domain, not the PCNA-binding domain, is solely responsible for the replication-coupled DNA methylation. Furthermore, the RFTS domain acts as a safety lock by protecting the genome from replication-independent DNA methylation.
Related Links	http://dx.doi.org/10.1371/journal.pone.0137509
Starting Page	137509
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	9
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-09-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1*

The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1

Aberrant DNA Methylation in ES Cells

Elucidating the Landscape of Aberrant DNA Methylation in Hepatocellular Carcinoma

Aberrant DNA Methylation: Implications in Racial Health Disparity

Transcriptional Repressive H3K9 and H3K27 Methylations Contribute to DNMT1-Mediated DNA Methylation Recovery

The RFTS Domain of Raf2 Is Required for Cul4 Interaction and Heterochromatin Integrity in Fission Yeast

Aberrant DNA Methylation of Matrix Remodeling and Cell Adhesion Related Genes in Pterygium

Genome-Wide Mapping of DNA Methylation in Chicken

Dual Functions of the RFTS Domain of Dnmt1 in Replication-Coupled DNA Methylation and in Protection of the Genome from Aberrant Methylation

Similar Documents

The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1*

The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1

Aberrant DNA Methylation in ES Cells

Elucidating the Landscape of Aberrant DNA Methylation in Hepatocellular Carcinoma

Aberrant DNA Methylation: Implications in Racial Health Disparity

Transcriptional Repressive H3K9 and H3K27 Methylations Contribute to DNMT1-Mediated DNA Methylation Recovery

The RFTS Domain of Raf2 Is Required for Cul4 Interaction and Heterochromatin Integrity in Fission Yeast

Aberrant DNA Methylation of Matrix Remodeling and Cell Adhesion Related Genes in Pterygium

Genome-Wide Mapping of DNA Methylation in Chicken

Dual Functions of the RFTS Domain of Dnmt1 in Replication-Coupled DNA Methylation and in Protection of the Genome from Aberrant Methylation