Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs

Cell
John L RinnHoward Y Chang

Abstract

Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kilobases. HOX ncRNAs are spatially expressed along developmental axes and possess unique sequence motifs, and their expression demarcates broad chromosomal domains of differential histone methylation and RNA polymerase accessibility. We identified a 2.2 kilobase ncRNA residing in the HOXC locus, termed HOTAIR, which represses transcription in trans across 40 kilobases of the HOXD locus. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.

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Feb 22, 2013·Molecular Biology of the Cell·Alexandre Jose Christino QuaresmaJeffrey A Nickerson
Dec 3, 2014·Trends in Cell Biology·Sofia Quinodoz, Mitchell Guttman
Sep 1, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiaoqiang GuoKaiyuan Deng
Mar 8, 2014·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Midie XuXiang Du
Feb 23, 2013·RNA·Neil Brockdorff
Jul 11, 2014·World Journal of Gastroenterology : WJG·Jun HanZhen-Yu He
Mar 19, 2011·Current Opinion in Cardiology·Apurva V Shirodkar, Philip A Marsden
Feb 9, 2012·Cellular and Molecular Life Sciences : CMLS·Carolina N PerdigotoElena Ezhkova
Mar 15, 2012·Cellular and Molecular Life Sciences : CMLS·Bing-Xue Yan, Jin-Xia Ma
Apr 17, 2013·Cellular and Molecular Life Sciences : CMLS·Ivan ContePaola Bovolenta
Nov 10, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Randall S Gieni, Michael J Hendzel
May 22, 2009·Neuromolecular Medicine·Rory Johnson, Noel J Buckley
Mar 29, 2008·Science·Paulo P AmaralJohn S Mattick
Feb 18, 2016·Genome Biology·David G HendricksonJohn L Rinn
Jan 20, 2016·Nature Reviews. Genetics·Ekta KhuranaMark Gerstein
Feb 19, 2016·Science Translational Medicine·Janika ViereckThomas Thum
Feb 18, 2016·Molecular Genetics and Genomics : MGG·Ruifang WuQianjin Lu
Feb 18, 2016·Genomics, Proteomics & Bioinformatics·Yiwen Fang, Melissa J Fullwood
Apr 21, 2009·FEBS Letters·Robert S Illingworth, Adrian P Bird
Jan 3, 2016·Experimental Cell Research·Ying-Fei LuJin-fang Zhang
Nov 21, 2015·Nucleic Acids Research·Yi ZhaoRunsheng Chen
Nov 7, 2014·Viruses·Mel CampbellYoshihiro Izumiya
Feb 20, 2008·Expert Review of Proteomics·Clemens BönischSandra B Hake
Oct 5, 2011·The Journal of Cell Biology·Howard Y Chang
Mar 13, 2013·Expert Review of Molecular Diagnostics·Katrien Van RoosbroeckGeorge Adrian Calin
Oct 22, 2014·International Journal of Molecular Sciences·Yanlan YaoLunan Wang
Jul 18, 2015·Genes·Stefania Del PreteValérie Gaudin
Feb 16, 2016·Cellular Signalling·Shanshan SunXuan Zhou
May 9, 2012·Expert Opinion on Drug Discovery·Deeksha BhartiyaVinod Scaria
May 23, 2013·Expert Opinion on Biological Therapy·Nicola AmodioPierfrancesco Tassone
Aug 30, 2014·Expert Opinion on Drug Metabolism & Toxicology·April K MarroneIgor P Pogribny
Dec 25, 2008·Critical Reviews in Biochemistry and Molecular Biology·James A Goodrich, Jennifer F Kugel
May 12, 2011·FEBS Letters·John S Mattick
May 18, 2011·FEBS Letters·Carolina Prezioso, Valerio Orlando
Apr 12, 2011·FEBS Letters·Ngai Cheung, Chi Wai Eric So
Aug 26, 2014·Journal of Molecular and Cellular Cardiology·Samir OunzainThierry Pedrazzini
Feb 11, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Michael SandSchapoor Hessam
Aug 5, 2015·Molecular Medicine Reports·Xin Yu, Zheng Li
Apr 1, 2015·Molecular Medicine Reports·Yu WangPeiling Li
Jan 1, 2015·BMC Systems Biology·Qingyang ZhangJi-Ping Wang
Jan 7, 2015·Journal of Cellular Biochemistry·Mazhar AdliSamir S El-Dahr
Jan 26, 2016·Biochemical and Biophysical Research Communications·Hongwei WuZhenguang Li
Jan 29, 2016·Current Opinion in Genetics & Development·Eric A Alcid, Toshio Tsukiyama
Feb 6, 2015·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Jie HuangLinlang Guo
Mar 18, 2016·Current Molecular Biology Reports·Jonathan Christopher DubéJosée Dostie
Feb 3, 2016·Biochemistry·Cigall KadochHeike Keilhack
Sep 25, 2015·Nucleic Acids Research·Stéphanie Maupetit-MéhouasPhilippe Arnaud
Aug 5, 2015·Virus Research·Buhle MoyoPatrick B Arbuthnot
Feb 4, 2016·Journal of the American Society of Nephrology : JASN·Wang ZhengXing-Zhen Chen
Sep 1, 2015·Virus Research·Sara Landeras-Bueno, Juan Ortín
Sep 3, 2014·Journal of Molecular Biology·Danling ZhuCaroline Dean
Jan 31, 2016·Genomics·Yao-zhong DingYong-guang Zhang
Nov 13, 2013·Nucleic Acids Research·Jiao YuanRunsheng Chen
Nov 29, 2013·Nucleic Acids Research·Chaoyong XieYi Zhao
Dec 25, 2015·Journal of Molecular Neuroscience : MN·James D MillsMichael Janitz
Dec 3, 2014·Pharmacology & Therapeutics·Brian S ComerWilliam T Gerthoffer
Dec 18, 2013·Neuroscience·K Schaukowitch, T-K Kim
Jan 8, 2011·Protein & Cell·Amanda Jones, Hengbin Wang
Jan 26, 2016·International Journal of Molecular Sciences·Kun YanAirong Qian
Dec 10, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Lukas VrbaBernard W Futscher
Jul 6, 2014·Nucleic Acids Research·Chen DavidovichThomas R Cech
Mar 10, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Mustafa Isin, Nejat Dalay
Dec 22, 2015·Journal of Biotechnology·Aizhan TastanovaMartin Fussenegger
Jul 3, 2013·Journal of Molecular Biology·John E FrobergJeannie T Lee
Jul 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yang WangGucheng Zeng
Dec 11, 2014·Journal of Hematology & Oncology·Gregory LoewenBin Shan
Dec 17, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ramiro GarzonClara D Bloomfield
Sep 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Gero DooseIngram Iaccarino
Jun 5, 2015·Briefings in Bioinformatics·Fabrizio FerrèManuela Helmer-Citterich
Apr 29, 2015·International Journal of Cardiology·Yidi MaBenzhi Cai
Apr 16, 2013·Analytical Biochemistry·Sivan TzadokIris Dotan
Jan 17, 2016·Seminars in Cell & Developmental Biology·Gregory A Quaife-RyanJames E Hudson
Dec 10, 2015·Journal of Assisted Reproduction and Genetics·Xin HuangHuangguan Dai
Feb 5, 2013·Journal of Molecular Biology·Arunoday BhanSubhrangsu S Mandal
May 7, 2013·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Quan Zhang, Kuan-Teh Jeang
Aug 27, 2015·Experimental Dermatology·Samantha M BeasleyIrene M Pedersen
Nov 28, 2012·Journal of Molecular Biology·Je-Hyun YoonMyriam Gorospe
Oct 31, 2015·Molecular Reproduction and Development·David H TaylorPaul D Soloway
Jul 13, 2012·Trends in Genetics : TIG·Robert IetswaartCaroline Dean
Jan 13, 2015·Science China. Life Sciences·Yin ZhangLiang-Hu Qu
Aug 14, 2009·The Journal of Investigative Dermatology. Symposium Proceedings·Yuji YamaguchiVincent J Hearing
May 24, 2012·Seminars in Nephrology·Alisha JamalPhilip A Marsden
May 1, 2012·Trends in Genetics : TIG·Marco MagistriClaes Wahlestedt
Feb 4, 2012·Trends in Biochemical Sciences·Jennifer F Kugel, James A Goodrich
Dec 20, 2011·Current Opinion in Genetics & Development·Vincenzo Pirrotta, Hua-Bing Li
Dec 14, 2011·Current Opinion in Genetics & Development·Ryan A Flynn, Howard Y Chang
Nov 15, 2011·Current Opinion in Plant Biology·Dong-Hwan Kim, Sibum Sung
Aug 15, 2014·Genome Biology·Nicole M WhiteChristopher A Maher
Nov 23, 2011·Trends in Plant Science·Eun-Deok Kim, Sibum Sung
Feb 18, 2016·Stem Cells International·Shanshan Hu, Ge Shan
May 3, 2013·Protein & Cell·Yeqing Angela Yang, Jindan Yu
Aug 13, 2011·Trends in Genetics : TIG·Ulf Andersson Orom, Ramin Shiekhattar
Jul 29, 2011·Trends in Genetics : TIG·Frédéric Bantignies, Giacomo Cavalli
Nov 19, 2010·The Journal of Investigative Dermatology·Richard L EckertSivaprakasam Balasubramanian
May 24, 2011·Trends in Genetics : TIG·Wu WeiLars M Steinmetz
May 17, 2011·Drug Discovery Today·Christopher A Hamm, Fabrício F Costa
Apr 5, 2011·Biochimica Et Biophysica Acta·Michael GroszmannW James Peacock
Feb 19, 2011·Current Opinion in Genetics & Development·Ulf Andersson Ørom, Ramin Shiekhattar
Feb 25, 2011·Seminars in Cell & Developmental Biology·Chandrasekhar Kanduri
Feb 19, 2011·Current Opinion in Plant Biology·Binglian Zheng, Xuemei Chen
Feb 19, 2011·Journal of Molecular Biology·Philippe Clerc, Philip Avner
Feb 22, 2011·Seminars in Cell & Developmental Biology·Ahmad M Khalil, John L Rinn
Sep 2, 2015·Biochimica Et Biophysica Acta·Amanda J BlytheCharles S Bond
Aug 25, 2015·Biochimica Et Biophysica Acta·Brian S Gloss, Marcel Dinger
Dec 21, 2010·Current Opinion in Plant Biology·Filomena De Lucia, Caroline Dean
Jan 25, 2011·Seminars in Cell & Developmental Biology·Michael B Clark, John S Mattick
Jun 27, 2015·Biochimica Et Biophysica Acta·Sarfraz ShafiqQianwen Sun
Jun 29, 2015·Biochimica Et Biophysica Acta·Shinichi Nakagawa