Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology

Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1

Danny Leung, Tingting Du, Ulrich Wagner, Wei Xie, Ah Young Lee, Preeti Goyal, Yujing Li, Keith E. Szulwach, Peng Jin, Matthew C. Lorincz, and Bing Ren
PNAS May 6, 2014 111 (18) 6690-6695; published ahead of print April 22, 2014 https://doi.org/10.1073/pnas.1322273111
Danny Leung
aLudwig Institute for Cancer Research, andbDepartment of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093-0653;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tingting Du
aLudwig Institute for Cancer Research, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ulrich Wagner
aLudwig Institute for Cancer Research, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Xie
cTsinghua University–Peking University Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ah Young Lee
aLudwig Institute for Cancer Research, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Preeti Goyal
dDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yujing Li
eDepartment of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keith E. Szulwach
eDepartment of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peng Jin
eDepartment of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew C. Lorincz
dDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: biren@ucsd.edumlorincz@mail.ubc.ca
Bing Ren
aLudwig Institute for Cancer Research, andbDepartment of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093-0653;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: biren@ucsd.edumlorincz@mail.ubc.ca
  1. Edited by Mark Groudine, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved April 1, 2014 (received for review November 28, 2013)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

DNA methylation is essential for mammalian development. This modification is nearly completely erased and reestablished in early embryos, but specific classes of DNA elements escape such genome-wide changes via unknown mechanisms. In this study, we identified a likely factor responsible for lack of DNA methylation turnover on a large fraction of such sequences. By focusing on mouse embryonic stem cells depleted of de novo DNA methyltransferases, which exhibit widespread hypomethylation with the exception of particular loci, we show that regions retaining DNA methylation are associated with a specific chromatin state. In cells lacking the enzyme catalyzing this chromatin state, such regions begin to lose DNA methylation. Our results therefore advance the understanding of how DNA methylation turnover is regulated during development.

Abstract

During mammalian development, DNA methylation patterns need to be reset in primordial germ cells (PGCs) and preimplantation embryos. However, many LTR retrotransposons and imprinted genes are impervious to such global epigenetic reprogramming via hitherto undefined mechanisms. Here, we report that a subset of such genomic regions are resistant to widespread erasure of DNA methylation in mouse embryonic stem cells (mESCs) lacking the de novo DNA methyltransferases (Dnmts) Dnmt3a and Dnmt3b. Intriguingly, these loci are enriched for H3K9me3 in mESCs, implicating this mark in DNA methylation homeostasis. Indeed, deletion of the H3K9 methyltransferase SET domain bifurcated 1 (Setdb1) results in reduced H3K9me3 and DNA methylation levels at specific loci, concomitant with increased 5-hydroxymethylation (5hmC) and ten-eleven translocation 1 binding. Taken together, these data reveal that Setdb1 promotes the persistence of DNA methylation in mESCs, likely reflecting one mechanism by which DNA methylation is maintained at LTR retrotransposons and imprinted genes during developmental stages when DNA methylation is reprogrammed.

  • epigenomics
  • histone modifications
  • repetitive elements
  • 5-hydroxymethylcytosine

Footnotes

  • ↵1D.L., T.D., and U.W. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. E-mail: biren{at}ucsd.edu or mlorincz{at}mail.ubc.ca.
  • Author contributions: D.L., T.D., U.W., W.X., P.J., M.C.L., and B.R. designed research; D.L., T.D., A.Y.L., P.G., Y.L., and K.E.S. performed research; Y.L., K.E.S., and P.J. contributed new reagents/analytic tools; D.L., U.W., and W.X. analyzed data; and D.L., T.D., U.W., W.X., M.C.L., and B.R. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE47894).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1322273111/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
Citation Tools
H3K9 trimethylation inhibits DNA demethylation
Danny Leung, Tingting Du, Ulrich Wagner, Wei Xie, Ah Young Lee, Preeti Goyal, Yujing Li, Keith E. Szulwach, Peng Jin, Matthew C. Lorincz, Bing Ren
Proceedings of the National Academy of Sciences May 2014, 111 (18) 6690-6695; DOI: 10.1073/pnas.1322273111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
H3K9 trimethylation inhibits DNA demethylation
Danny Leung, Tingting Du, Ulrich Wagner, Wei Xie, Ah Young Lee, Preeti Goyal, Yujing Li, Keith E. Szulwach, Peng Jin, Matthew C. Lorincz, Bing Ren
Proceedings of the National Academy of Sciences May 2014, 111 (18) 6690-6695; DOI: 10.1073/pnas.1322273111
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 116 (8)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

News Feature: Cities serve as testbeds for evolutionary change
Urban living can pressure flora and fauna to adapt in intriguing ways. Biologists are starting to take advantage of this convenient laboratory of evolution.
Image credit: Kristin Winchell (Washington University in St. Louis, St. Louis).
Several aspects of the proposal, which aims to expand open access, require serious discussion and, in some cases, a rethink.
Opinion: “Plan S” falls short for society publishers—and for the researchers they serve
Several aspects of the proposal, which aims to expand open access, require serious discussion and, in some cases, a rethink.
Image credit: Dave Cutler (artist).
Featured Profile
PNAS Profile of NAS member and biochemist Hao Wu
 Nonmonogamous strawberry poison frog (Oophaga pumilio).  Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Putative signature of monogamy
A study suggests a putative gene-expression hallmark common to monogamous male vertebrates of some species, namely cichlid fishes, dendrobatid frogs, passeroid songbirds, common voles, and deer mice, and identifies 24 candidate genes potentially associated with monogamy.
Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Active lifestyles. Image courtesy of Pixabay/MabelAmber.
Meaningful life tied to healthy aging
Physical and social well-being in old age are linked to self-assessments of life worth, and a spectrum of behavioral, economic, health, and social variables may influence whether aging individuals believe they are leading meaningful lives.
Image courtesy of Pixabay/MabelAmber.

More Articles of This Classification

Biological Sciences

  • Photosynthetic adaptation to low iron, light, and temperature in Southern Ocean phytoplankton
  • DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration
  • Calcineurin dephosphorylates Kelch-like 3, reversing phosphorylation by angiotensin II and regulating renal electrolyte handling
Show more

Genetics

  • Processing generates 3′ ends of RNA masking transcription termination events in prokaryotes
  • Self-regulation and the foraging gene (PRKG1) in humans
  • The ubiquitin ligase UBE3B, disrupted in intellectual disability and absent speech, regulates metabolic pathways by targeting BCKDK
Show more

Related Content

  • No related articles found.
  • Scopus
  • PubMed
  • Google Scholar

Cited by...

  • KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control
  • Selfish DNA and Epigenetic Repression Revisited
  • Epigenetic dynamics during preimplantation development
  • MPE-seq, a new method for the genome-wide analysis of chromatin structure
  • Atrx promotes heterochromatin formation at retrotransposons
  • DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination
  • ZFP57 and the Targeted Maintenance of Postfertilization Genomic Imprints
  • Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells
  • Scopus (38)
  • Google Scholar

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Classics
  • Front Matter
  • Teaching Resources
  • Anthropology
  • Chemistry
  • Physics
  • Sustainability Science

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Press
  • Site Map

Feedback    Privacy/Legal

Copyright © 2019 National Academy of Sciences. Online ISSN 1091-6490