Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain

Genome Biology
Lu WenJie Qiao

Abstract

5-methylcytosine (mC) can be oxidized by the tet methylcytosine dioxygenase (Tet) family of enzymes to 5-hydroxymethylcytosine (hmC), which is an intermediate of mC demethylation and may also be a stable epigenetic modification that influences chromatin structure. hmC is particularly abundant in mammalian brains but its function is currently unknown. A high-resolution hydroxymethylome map is required to fully understand the function of hmC in the human brain. We present genome-wide and single-base resolution maps of hmC and mC in the human brain by combined application of Tet-assisted bisulfite sequencing and bisulfite sequencing. We demonstrate that hmCs increase markedly from the fetal to the adult stage, and in the adult brain, 13% of all CpGs are highly hydroxymethylated with strong enrichment at genic regions and distal regulatory elements. Notably, hmC peaks are identified at the 5'splicing sites at the exon-intron boundary, suggesting a mechanistic link between hmC and splicing. We report a surprising transcription-correlated hmC bias toward the sense strand and an mC bias toward the antisense strand of gene bodies. Furthermore, hmC is negatively correlated with H3K27me3-marked and H3K9me3-marked repressive genomic regio...Continue Reading

References

Mar 1, 1995·Trends in Genetics : TIG·A P Bird
May 1, 1993·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C Redies, M Takeichi
Feb 27, 2007·Science·Asaf Hellman, Andrew Chess
Jan 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John D CahoyBen A Barres
Apr 30, 2008·BMC Neuroscience·Yan JiangSchahram Akbarian
Jan 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Tibor A RauchGerd P Pfeifer
Mar 31, 2009·Nature Biotechnology·Madeleine P BallGeorge M Church
Apr 18, 2009·Science·Skirmantas Kriaucionis, Nathaniel Heintz
Feb 6, 2010·Genome Research·Louise LaurentChia-Lin Wei
Apr 17, 2010·Science·Assaf ZemachDaniel Zilberman
Jun 1, 2010·Nature·Ramakrishna K ChodavarapuMatteo Pellegrini
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Menno P CreyghtonRudolf Jaenisch
Mar 8, 2011·Nucleic Acids Research·Seung-Gi JinGerd P Pfeifer
Apr 15, 2011·Nature·Kristine WilliamsKristian Helin
May 10, 2011·Nature·William A PastorAnjana Rao
Oct 21, 2011·Nature·David BrawandHenrik Kaessmann
Nov 1, 2011·Nature Neuroscience·Keith E SzulwachPeng Jin
May 30, 2012·Nature Reviews. Genetics·Peter A Jones
Sep 11, 2012·Nature Structural & Molecular Biology·Tarang KhareArturas Petronis
Dec 1, 2012·Nature Protocols·Miao YuChuan He
Feb 26, 2013·Cell·Cornelia G SpruijtMichiel Vermeulen
Mar 19, 2013·Cell·Ulrich BraunschweigBenjamin J Blencowe
Jun 19, 2013·Cell Stem Cell·Run-Rui ZhangGuo-Liang Xu
Jul 3, 2013·Trends in Genetics : TIG·Eli Eisenberg, Erez Y Levanon
Jul 6, 2013·Science·Ryan ListerJoseph R Ecker

Citations

Sep 28, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Irfan A Qureshi, Mark F Mehler
Jan 14, 2016·Critical Reviews in Clinical Laboratory Sciences·Laila C SchenkelBekim Sadikovic
Feb 2, 2016·Schizophrenia Research·John F FullardPanos Roussos
Mar 6, 2015·Proceedings of the National Academy of Sciences of the United States of America·Benyam KindeMichael E Greenberg
May 10, 2015·Pharmacology & Therapeutics·Kristen M Meldi, Maria E Figueroa
Jan 7, 2016·Frontiers in Behavioral Neuroscience·Jose V Sanchez-Mut, Johannes Gräff
Mar 13, 2016·Blood Reviews·Benjamin E PaluchElizabeth A Griffiths
Nov 28, 2015·Nucleic Acids Research·Alexey KozlenkovStella Dracheva
Jun 28, 2015·Gene·Shariq I Sherwani, Haseeb A Khan
Mar 10, 2016·Human Molecular Genetics·Rebecca A G De SouzaBlair R Leavitt
Dec 17, 2014·Immunological Reviews·Erika L MoenLucy A Godley
Oct 25, 2014·BMB Reports·Guo-Liang Xu, Colum P Walsh
Jun 5, 2015·Human Molecular Genetics·Sruti ChandraMelanie Ehrlich
Jun 26, 2015·Epigenomics·Christiaan H VinkersMarco P M Boks
Jun 26, 2015·Epigenomics·David P GavinSubhash C Pandey
Mar 31, 2015·Nucleic Acids Research·Qing LiJohn M Greally
Mar 7, 2015·Molecular Biology and Evolution·Avazeh T Ghanbarian, Laurence D Hurst
May 16, 2015·Epigenetics & Chromatin·Pau FarréMichael S Kobor
Mar 27, 2015·Nature Neuroscience·Anne E West
Sep 3, 2014·Genomics·Maria A HahnGerd P Pfeifer
Dec 23, 2014·Epigenomics·Melanie Ehrlich, Kenneth C Ehrlich
Nov 29, 2014·Epigenomics·Euan J RodgerIan M Morison
May 6, 2016·BMC Genomics·Martijn F L DerksKees van Oers
May 7, 2016·Nature Reviews. Neuroscience·Annie Vogel Ciernia, Janine LaSalle
Jun 9, 2016·Behavioral and Brain Functions : BBF·Galina Y ZheleznyakovaHelgi B Schiöth
Jun 21, 2016·Epigenomics·Rachelle E IrwinColum P Walsh
May 18, 2016·ELife·Marketa TomkovaBenjamin Schuster-Böckler
Jul 8, 2016·Scientific Reports·Jianshi JinXiao-Dong Su
Jul 10, 2016·Journal of Translational Medicine·Estela G TorañoAgustin F Fernandez
Jul 18, 2016·Trends in Molecular Medicine·Hans-Ulrich Klein, Philip L De Jager
Aug 5, 2016·Nature Communications·Carolina M GrecoGianluigi Condorelli
Sep 23, 2016·Biochemistry·Crystal M Vander ZandenP Shing Ho
Oct 14, 2016·Epigenomics·Moshe Szyf
Oct 22, 2016·Journal of the American Chemical Society·Gosuke HayashiAkimitsu Okamoto
Nov 26, 2016·Genes·Anke HoffmannDietmar Spengler
Dec 15, 2015·PLoS Genetics·Irene Hernando-HerraezTomas Marques-Bonet
May 5, 2017·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Rebecca M HauserFarah D Lubin
May 16, 2017·Genes·Maria Fasolino, Zhaolan Zhou
Apr 8, 2017·International Journal of Molecular Sciences·Ariel Ernesto Cariaga-Martínez, Raúl Alelú-Paz
May 31, 2017·Nature Reviews. Genetics·Xiaoji Wu, Yi Zhang
Sep 12, 2015·The Lancet. Psychiatry·Gustavo TureckiJoan Kaufman
Aug 4, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·Syed Khund-SayeedCharles Vinson
Jul 6, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Jose Ramon Hernandez MoraDavid Monk
Mar 3, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Carl BaribaultMelanie Ehrlich
Feb 17, 2018·Frontiers in Neuroscience·Stefan H Stricker, Magdalena Götz
Sep 4, 2017·Journal of Molecular Neuroscience : MN·Elizabeth M EllisonMark A Lovell
Nov 14, 2017·Epigenomics·John P ThomsonRichard R Meehan
Sep 26, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Qin MaWeimin Ci
Jun 8, 2018·Human Molecular Genetics·Agustin F FernandezMario F Fraga
Aug 7, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Joseph KochmanskiDana C Dolinoy
Jan 30, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Benjamin V BeckerReinhard Ullmann
Mar 15, 2019·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Mohammed ArifElaine M Urbina
Sep 12, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Nicholas D JohnsonKaren N Conneely
Jul 10, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Melanie Ehrlich
Dec 18, 2019·Essays in Biochemistry·Ksenia SkvortsovaPhillippa Taberlay
Dec 14, 2019·Aging Cell·Luigi FerrucciRafael de Cabo
Mar 3, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Yi ZhangMei Zhong
Apr 28, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benjamin B GreenCarmen J Marsit
Jul 11, 2019·Genome Biology·Isabel MendizabalSoojin V Yi
Oct 31, 2015·Genes, Brain, and Behavior·Cathy L Barr, Virginia L Misener
Dec 3, 2016·Epigenetics : Official Journal of the DNA Methylation Society·V K Chaithanya PonnaluriMelanie Ehrlich
Feb 24, 2017·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Adrian ZhubiDennis R Grayson
May 17, 2018·Brain Plasticity·Emily M Jobe, Xinyu Zhao
Aug 2, 2018·Frontiers in Genetics·Juan P JiménezPatrick Luyten
Mar 13, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Joseph KochmanskiAlison I Bernstein
Dec 18, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Owen M WilkinsBrock C Christensen
May 5, 2018·International Journal of Molecular Sciences·Ariel Ernesto Cariaga-MartínezRaúl Alelú-Paz
Jun 30, 2018·Molecular Psychiatry·Gabor EgervariYasmin L Hurd
Jan 19, 2020·Scientific Reports·Santiago Uribe-LewisAdele Murrell
Dec 4, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Paiyun LiDajun Deng
May 9, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Kahlilia C Morris-BlancoRaghu Vemuganti
Jan 18, 2017·Current Behavioral Neuroscience Reports·Kelly M BakulskiM Daniele Fallin
Nov 29, 2016·Frontiers in Cellular and Infection Microbiology·Weiwei Liu
Sep 20, 2017·BMC Genomics·Helen SpiersJonathan Mill
Feb 6, 2020·Current Environmental Health Reports·Joseph Kochmanski, Alison I Bernstein
May 19, 2017·Epigenomics·Renaud MassartMoshe Szyf
Dec 22, 2017·Organic & Biomolecular Chemistry·M RavichandranT P Jurkowski
Jul 20, 2018·Frontiers in Medicine·Nuria Oliva-VilarnauVolker M Lauschke
Jun 23, 2018·Journal of Molecular Neuroscience : MN·Melisa C MonteleoneMarcela A Brocco
Jan 17, 2019·Nucleic Acids Research·Christopher E SchlosbergJohn R Edwards
Oct 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yogini P Bhavsar-JogRandy M Wadkins
Dec 16, 2019·Neurochemistry International·Mario J BertogliatRaghu Vemuganti
Dec 24, 2019·Journal of Molecular Biology·Cathia RauschM Cristina Cardoso
Jan 30, 2021·Seminars in Cell & Developmental Biology·Albert T Higgins-ChenMorgan E Levine
Feb 9, 2021·Frontiers in Genetics·Katrina V GoodJuan Ausió
Nov 21, 2020·Communications Biology·Ana J Chucair-ElliottWillard M Freeman
Apr 2, 2021·Nature Communications·Hyeonsoo JeongSoojin V Yi

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