Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation.

Nucleic Acids Research
Hideharu HashimotoXiaodong Cheng

Abstract

Cytosine residues in mammalian DNA occur in at least three forms, cytosine (C), 5-methylcytosine (M; 5mC) and 5-hydroxymethylcytosine (H; 5hmC). During semi-conservative DNA replication, hemi-methylated (M/C) and hemi-hydroxymethylated (H/C) CpG dinucleotides are transiently generated, where only the parental strand is modified and the daughter strand contains native cytosine. Here, we explore the role of DNA methyltransferases (DNMT) and ten eleven translocation (Tet) proteins in perpetuating these states after replication, and the molecular basis of their recognition by methyl-CpG-binding domain (MBD) proteins. Using recombinant proteins and modified double-stranded deoxyoligonucleotides, we show that DNMT1 prefers a hemi-methylated (M/C) substrate (by a factor of >60) over hemi-hydroxymethylated (H/C) and unmodified (C/C) sites, whereas both DNMT3A and DNMT3B have approximately equal activity on all three substrates (C/C, M/C and H/C). Binding of MBD proteins to methylated DNA inhibited Tet1 activity, suggesting that MBD binding may also play a role in regulating the levels of 5hmC. All five MBD proteins generally have reduced binding affinity for 5hmC relative to 5mC in the fully modified context (H/M versus M/M), though th...Continue Reading

References

Nov 24, 2001·Science·D Bourc'hisT H Bestor
Dec 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Frederic ChedinChih-Lin Hsieh
Apr 24, 2004·The Journal of Biological Chemistry·Isao SuetakeShoji Tajima
Aug 20, 2004·Nature·Déborah Bourc'his, Timothy H Bestor
Jan 27, 2005·The Journal of Biological Chemistry·Humaira GowherAlbert Jeltsch
May 26, 2005·Protein Expression and Purification·F William Studier
Jul 11, 2006·The Journal of Biological Chemistry·Michael S KaretaFrédéric Chédin
Aug 4, 2007·Science·Magnolia BostickSteven E Jacobsen
Mar 13, 2008·Structure·Xiaodong Cheng, Robert M Blumenthal
Aug 30, 2008·Biochemistry·Mihika PradhanSriharsa Pradhan
Sep 6, 2008·Nature·Hideharu HashimotoXiaodong Cheng
Oct 24, 2008·The Journal of Biological Chemistry·Chengmin QianMing-Ming Zhou
Apr 18, 2009·Science·Skirmantas Kriaucionis, Nathaniel Heintz
Jul 22, 2009·Molecular and Cellular Biology·Shinwu JeongPeter A Jones
Oct 1, 2009·Nature Reviews. Genetics·Peter A Jones, Gangning Liang
Dec 23, 2009·Nucleic Acids Research·Andrea RottachHeinrich Leonhardt
Dec 15, 2010·Nature Structural & Molecular Biology·Pierre-Olivier EstèveSriharsa Pradhan

❮ Previous
Next ❯

Citations

Sep 3, 2013·DNA Repair·Ángel Ramiro-MerinaTeresa Roldán-Arjona
Aug 21, 2013·Neuropharmacology·David P GavinRajiv P Sharma
Jun 7, 2013·Journal of Human Genetics·Takashi Kohda
May 31, 2013·Journal of Human Genetics·Hongbo Zhao, Taiping Chen
Sep 6, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Dennis R Grayson, Alessandro Guidotti
Dec 1, 2012·Nature Protocols·Miao YuChuan He
May 24, 2013·Nature Reviews. Molecular Cell Biology·William A PastorAnjana Rao
Mar 7, 2013·Nature Structural & Molecular Biology·Yehudit Bergman, Howard Cedar
Jul 31, 2012·Chemical Society Reviews·Edita KriukienėSaulius Klimašauskas
Aug 18, 2012·The Journal of Biological Chemistry·Chun-Chang ChenChe-Kun James Shen
Jun 28, 2013·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Dina BellizziGiuseppe Passarino
May 3, 2013·Epigenetics & Chromatin·Gerd P PfeiferSeung-Gi Jin
May 10, 2012·Development·Li Tan, Yujiang Geno Shi
Jan 5, 2014·PLoS Genetics·Takashi ShimboPaul A Wade
Aug 24, 2012·PloS One·Gopinath RangamSvend K Petersen-Mahrt
Jul 23, 2013·International Journal of Molecular Sciences·Yannick DelpuJérôme Torrisani
Aug 6, 2013·Cellular and Molecular Life Sciences : CMLS·Bing Yao, Peng Jin
Nov 29, 2013·Epigenomics·Alexander LairdRichard R Meehan
Sep 21, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Björn Tampe, Michael Zeisberg
Oct 15, 2013·Trends in Cell Biology·Francesco M Piccolo, Amanda G Fisher
Dec 18, 2013·Nature Structural & Molecular Biology·Ofra SabagHoward Cedar
May 13, 2014·Cell and Tissue Research·Gerd P PfeiferSeung-Gi Jin
Jun 7, 2014·Annual Review of Biochemistry·Li ShenYi Zhang
May 28, 2014·Journal of Molecular Modeling·André GrandLeif A Eriksson
Oct 15, 2014·Seminars in Hematology·Ashley M Perry, Eyal C Attar
Jan 24, 2013·Cellular and Molecular Life Sciences : CMLS·Hillary F AllenTatiana G Kutateladze
Feb 15, 2016·Current Opinion in Genetics & Development·Jana JeschkeFrançois Fuks
Oct 24, 2014·Biology·Vichithra R B LiyanageJames R Davie

❮ Previous
Next ❯

Methods Mentioned

BETA
deamination
electrophoresis
glycosylation
glycosylase

Software Mentioned

GraphPad
GraphPad PRISM

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.