DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells

Genome Biology
Tianpeng GuMargaret A Goodell

Abstract

DNA methylation is a heritable epigenetic mark, enabling stable but reversible gene repression. In mammalian cells, DNA methyltransferases (DNMTs) are responsible for modifying cytosine to 5-methylcytosine (5mC), which can be further oxidized by the TET dioxygenases to ultimately cause DNA demethylation. However, the genome-wide cooperation and functions of these two families of proteins, especially at large under-methylated regions, called canyons, remain largely unknown. Here we demonstrate that DNMT3A and TET1 function in a complementary and competitive manner in mouse embryonic stem cells to mediate proper epigenetic landscapes and gene expression. The longer isoform of DNMT3A, DNMT3A1, exhibits significant enrichment at distal promoters and canyon edges, but is excluded from proximal promoters and canyons where TET1 shows prominent binding. Deletion of Tet1 increases DNMT3A1 binding capacity at and around genes with wild-type TET1 binding. However, deletion of Dnmt3a has a minor effect on TET1 binding on chromatin, indicating that TET1 may limit DNA methylation partially by protecting its targets from DNMT3A and establishing boundaries for DNA methylation. Local CpG density may determine their complementary binding pattern...Continue Reading

Associated Datasets

May 16, 2018

References

Jun 23, 2001·Oncogene·K D Robertson
Jul 11, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Akiko TsumuraMasaki Okano
Jul 5, 2008·Nature·Alexander MeissnerEric S Lander
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jul 29, 2009·BMC Bioinformatics·Yuanxin Xi, Wei Li
Apr 15, 2011·Nature·Kristine WilliamsKristian Helin
Oct 25, 2011·Trends in Genetics : TIG·Sébastien A Smallwood, Gavin Kelsey
Jan 6, 2012·The New England Journal of Medicine·Lucile CouronnéOlivier A Bernard
Sep 29, 2012·Nature Protocols·Yun HuangAnjana Rao
Sep 26, 2013·Bioinformatics·Xueqiu LinWei Li
Nov 26, 2013·Nature Genetics·Mira JeongMargaret A Goodell
Feb 26, 2014·Genome Biology·Deqiang SunWei Li
Apr 17, 2014·Developmental Cell·Meelad M DawlatyRudolf Jaenisch
May 3, 2014·Cold Spring Harbor Perspectives in Biology·En Li, Yi Zhang
Aug 19, 2014·Cell Stem Cell·Grant A ChallenMargaret A Goodell
Sep 17, 2014·Genes & Development·Falong LuYi Zhang
Jul 21, 2015·Cell Reports·Matyas Flemr, Marc Bühler
Dec 3, 2015·Science·Ian M SlaymakerFeng Zhang
Aug 2, 2016·Cell Stem Cell·Lorenzo RinaldiSalvador Aznar Benitah

❮ Previous
Next ❯

Citations

Oct 3, 2019·Development·Orla Deevy, Adrian P Bracken
Nov 15, 2019·Essays in Biochemistry·Christian PfluegerRyan Lister
Oct 28, 2019·Cellular and Molecular Life Sciences : CMLS·Mafalda SantiagoC Joana Marques
Dec 10, 2019·Annual Review of Biochemistry·Zhiyuan Chen, Yi Zhang
May 6, 2019·Epigenetics & Chromatin·Henriette O'GeenDavid J Segal
Apr 25, 2019·Nature Communications·Gintarė SendžikaitėGavin Kelsey
Jul 25, 2019·Nucleic Acids Research·Mengchi WangWei Wang
Mar 25, 2020·Bioscience Reports·Matthew P HirakawaKimberly S Butler
Mar 10, 2020·F1000Research·Hannah Demond, Gavin Kelsey
Dec 14, 2018·Genes·Marthe LaisnéPierre-Antoine Defossez
Aug 3, 2019·Proceedings of the National Academy of Sciences of the United States of America·Isaac F López-MoyadoAnjana Rao
Aug 23, 2019·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Basavaraj SajjanarSiriluck Ponsuksili
Oct 2, 2019·Frontiers in Oncology·Alexander A Wurm, Cristina Pina
Oct 8, 2020·Nature Reviews. Genetics·Aled ParryWolf Reik
Nov 26, 2020·Nature Communications·Christopher B MulhollandHeinrich Leonhardt
Dec 9, 2020·Nucleic Acids Research·Izaskun MallonaTuncay Baubec
Jan 13, 2021·Briefings in Bioinformatics·Mengchi WangWei Wang
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Maxim V C Greenberg
Feb 2, 2021·Frontiers in Cell and Developmental Biology·Nikolas James TsiouplisAgeliki Tsagaratou
Apr 10, 2021·Science·Gary DixonDanwei Huangfu
Apr 10, 2021·Science·Tianpeng Gu, Margaret A Goodell
Mar 13, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Praveen KusumanchiSuthat Liangpunsakul
Oct 6, 2021·Nature Reviews. Genetics·Sanne M Janssen, Matthew C Lorincz
Oct 14, 2021·American Journal of Medical Genetics. Part a·Alana C CecchiDianna M Milewicz
Oct 21, 2021·ELife·Kevin R CostelloDustin E Schones

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
immunoprecipitation
dot blot
ChIP-seq
WGBS
transfection
genotyping
PCR
ChIP
DNA-seq

Software Mentioned

UCSC
Burrows
TopHat
DANPOS
MACS2
SAMtools
mComp
CSEM
Means R
MOABS

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.