The inherent processivity of the human de novo methyltransferase 3A (DNMT3A) is enhanced by DNMT3L.

The Journal of Biological Chemistry
Celeste Holz-Schietinger, Norbert O Reich

Abstract

Human DNMT3A is responsible for de novo DNA cytosine methylation patterning during development. Here we show that DNMT3A methylates 5-8 CpG sites on human promoters before 50% of the initially bound enzyme dissociates from the DNA. Processive methylation is enhanced 3-fold in the presence of DNMT3L, an inactive homolog of DNMT3A, therefore providing a mechanism for the previously described DNMT3L activation of DNMT3A. DNMT3A processivity on human promoters is also regulated by DNA topology, where a 2-fold decrease in processivity was observed on supercoiled DNA in comparison with linear DNA. These results are the first observation that DNMT3A utilizes this mechanism of increasing catalytic efficiency. Processive de novo DNA methylation provides a mechanism that ensures that multiple CpG sites undergo methylation for transcriptional regulation and silencing of newly integrated viral DNA.

References

Nov 30, 1992·FEBS Letters·P Renbaum, A Razin
Nov 1, 1989·Analytical Biochemistry·S C Gill, P H von Hippel
Nov 24, 1999·Molecular and Cellular Biology·C L Hsieh
Sep 27, 2000·Human Molecular Genetics·T H Bestor
Aug 11, 2001·Science·W ReikJ Walter
Aug 28, 2001·Nucleic Acids Research·A AokiS Tajima
Nov 24, 2001·Science·D Bourc'hisT H Bestor
Jan 10, 2002·Genes & Development·Adrian Bird
Mar 29, 2002·The Journal of Biological Chemistry·Humaira Gowher, Albert Jeltsch
Apr 5, 2002·Genome Research·Liora Z Strichman-AlmashanuAndrew P Feinberg
Apr 18, 2002·Current Opinion in Structural Biology·David JeruzalmiJohn Kuriyan
Apr 25, 2003·Nucleic Acids Research·François FuksTony Kouzarides
Jul 19, 2003·Journal of Biochemistry·Isao SuetakeShoji Tajima
Oct 23, 2003·Nature Reviews. Molecular Cell Biology·Nicola Haines, Kenneth D Irvine
Oct 28, 2003·The Journal of Biological Chemistry·Mitsuru Okuwaki, Alain Verreault
Feb 18, 2004·Molecular Cell·Michael FreitagEric U Selker
Apr 24, 2004·The Journal of Biological Chemistry·Isao SuetakeShoji Tajima
Aug 18, 2004·Biochemical and Biophysical Research Communications·Andrea K RobertsonKeith D Robertson
Oct 29, 2004·The Journal of Biological Chemistry·Giedrius VilkaitisShoji Tajima
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kylie E WebsterHamish S Scott
Aug 12, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Zhao-xia Chen, Arthur D Riggs
Sep 2, 2005·Nature Reviews. Genetics·Keith D Robertson
Nov 9, 2005·Biochemistry·Zeljko M Svedruzić, Norbert O Reich
Dec 3, 2005·Journal of Molecular Biology·Stacey N Peterson, Norbert O Reich
Mar 29, 2006·Journal of Biochemistry·Hideyuki TakeshimaShoji Tajima
Jun 9, 2006·Critical Reviews in Biochemistry and Molecular Biology·Linda B Bloom
Jul 11, 2006·The Journal of Biological Chemistry·Michael S KaretaFrédéric Chédin
Oct 31, 2006·Nature Genetics·Florian EckhardtStephan Beck
Dec 22, 2006·Traffic·Matthew A Berezuk, Trina A Schroer
Oct 30, 2007·Epigenetics : Official Journal of the DNA Methylation Society·Maja Klug, Michael Rehli
Oct 31, 2007·Molecular and Cellular Biology·Kevin Myant, Irina Stancheva
Feb 14, 2008·Current Topics in Microbiology and Immunology·Kevin V Morris
Mar 25, 2009·Nature Reviews. Genetics·Howard Cedar, Yehudit Bergman
Sep 30, 2009·Epigenetics : Official Journal of the DNA Methylation Society·Eric HervouetPierre-François Cartron

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Citations

Oct 15, 2010·Nature Biotechnology·Anna Portela, Manel Esteller
Oct 8, 2011·The Journal of Biological Chemistry·Celeste Holz-SchietingerNorbert O Reich
Jun 23, 2012·The Journal of Biological Chemistry·Celeste Holz-SchietingerNorbert O Reich
Mar 8, 2011·Nucleic Acids Research·Beth O Van Emburgh, Keith D Robertson
Jun 26, 2012·Nucleic Acids Research·Celeste Holz-Schietinger, Norbert O Reich
Jul 31, 2013·PloS One·Catherine A GordonFrédéric Chédin
Mar 13, 2012·World Journal of Gastroenterology : WJG·Xiang-Quan LiWei De
Jun 8, 2012·Biology of the Cell·Hung-Fu LiaoShau-Ping Lin
Apr 30, 2013·The Biochemical Journal·Alexandra PlotnikovaGiedrius Vilkaitis
Jul 30, 2015·BioMed Research International·Shan-Shan WuEr-Yuan Liao
Feb 17, 2015·Cell Reports·Georgios VlachogiannisSteen K T Ooi
Aug 8, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Rebecca P HabermanMichela Gallagher
Mar 5, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Bi-Feng Chen, Wai-Yee Chan
Jun 16, 2012·Mutation Research·Lien Van De VoordeMarijn Speeckaert
Feb 15, 2015·Biochimica Et Biophysica Acta·Celeste Holz-Schietinger, Norbert O Reich
Aug 16, 2016·Nucleic Acids Research·Albert Jeltsch, Renata Z Jurkowska
Jun 17, 2015·Annual Review of Genomics and Human Genetics·Yupeng He, Joseph R Ecker
Nov 3, 2016·Chembiochem : a European Journal of Chemical Biology·Clayton B WoodcockMikhail S Shchepinov
Jul 7, 2011·Current Protocols in Molecular Biology·Carolina E PardoMichael P Kladde
Sep 30, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Robert ShoemakerKun Zhang
Mar 14, 2017·BioMed Research International·Sabah F Chaudry, Timothy J T Chevassut
Feb 20, 2015·Nature Reviews. Cancer·Liubin YangMargaret A Goodell
Dec 22, 2017·Organic & Biomolecular Chemistry·M RavichandranT P Jurkowski
Sep 20, 2017·Genome Biology·Yung-Hsin HuangMargaret A Goodell
May 31, 2017·International Journal of Hematology·Hiroyoshi Kunimoto, Hideaki Nakajima
Aug 3, 2019·Cold Spring Harbor Molecular Case Studies·Elena I FomchenkoJennifer Moliterno
Feb 23, 2020·Nucleic Acids Research·Chien-Chu LinHanna S Yuan
Nov 12, 2020·The Journal of Biological Chemistry·Jonathan E Sandoval, Norbert O Reich

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