UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development

Nature
Karl AggerKristian Helin

Abstract

The trithorax and the polycomb group proteins are chromatin modifiers, which play a key role in the epigenetic regulation of development, differentiation and maintenance of cell fates. The polycomb repressive complex 2 (PRC2) mediates transcriptional repression by catalysing the di- and tri-methylation of Lys 27 on histone H3 (H3K27me2/me3). Owing to the essential role of the PRC2 complex in repressing a large number of genes involved in somatic processes, the H3K27me3 mark is associated with the unique epigenetic state of stem cells. The rapid decrease of the H3K27me3 mark during specific stages of embryogenesis and stem-cell differentiation indicates that histone demethylases specific for H3K27me3 may exist. Here we show that the human JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3. Furthermore, we demonstrate that ectopic expression of JMJD3 leads to a strong decrease of H3K27me3 levels and causes delocalization of polycomb proteins in vivo. Consistent with the strong decrease in H3K27me3 levels associated with HOX genes during differentiation, we show that UTX directly binds to the HOXB1 locus and is required for its activation. Finally mutation of F18E9.5, a Caenorhabditis ele...Continue Reading

References

Oct 17, 2008·Cellular and Molecular Life Sciences : CMLS·S S NgR J Klose
Dec 15, 2012·Diabetologia·B R TennantB G Hoffman
May 27, 2011·Human Genetics·Joel B BerletchChristine M Disteche
Aug 10, 2012·Clinical Oral Investigations·Gláucia de Camargo PereiraMarcelo Rocha Marques
Oct 6, 2009·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Carolyn A Bondy, Clara Cheng
Feb 5, 2010·Journal of Mammary Gland Biology and Neoplasia·Mathieu Dalvai, Kerstin Bystricky
Oct 17, 2012·Current Diabetes Reports·Hironori WakiTakashi Kadowaki
Jan 5, 2013·International Journal of Hematology·Ly P VuStephen D Nimer
Mar 19, 2014·International Journal of Cardiology·Pankaj Chaturvedi, Suresh C Tyagi
Aug 13, 2013·Molecular and Cellular Neurosciences·Berta HenriquezBrigitte van Zundert
Sep 2, 2010·Cell Stem Cell·Lauren E SurfaceLaurie A Boyer
Nov 3, 2010·Cell Stem Cell·Maria J BarreroJuan Carlos Izpisua Belmonte
May 19, 2011·Journal of the American Chemical Society·Xuelai LuoXiang Wang
Oct 1, 2011·Journal of Medicinal Chemistry·Takayoshi Suzuki, Naoki Miyata
Aug 15, 2008·Journal of Proteome Research·Benjamin A GarciaCraig A Mizzen
Oct 10, 2007·Cell Research·Yang XiangCharlie Degui Chen
Apr 13, 2012·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hyun-Min ChoIn Kyeom Kim
Jan 14, 2010·Leukemia·C AcquavivaD Birnbaum
Jun 23, 2012·Nature·Giles RobinsonRichard J Gilbertson
Sep 11, 2010·Nature Biotechnology·Carlo M Croce
Jan 23, 2009·Nature Cell Biology·Shiraz MujtabaMing-Ming Zhou
Oct 22, 2008·Nature Cell Biology·Klaus H HansenKristian Helin
May 24, 2011·Nature Cell Biology·Antonio AdamoJuan Carlos Izpisua Belmonte
Dec 18, 2013·Nature Communications·Donna DentonSharad Kumar
Mar 31, 2009·Nature Genetics·Gijs van HaaftenP Andrew Futreal
Jun 25, 2010·Nature Reviews. Cancer·Ping ChiGang Greg Wang
Apr 5, 2012·Nature Reviews. Molecular Cell Biology·Susanne Marije Kooistra, Kristian Helin
Jul 24, 2012·Nature Reviews. Molecular Cell Biology·Mo LiJuan Carlos Izpisua Belmonte
Nov 7, 2007·Nature Structural & Molecular Biology·Sukesh R BhaumikAli Shilatifard
Feb 21, 2013·Translational Psychiatry·S J JamesI P Pogribny
Mar 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Doug PhanstielJoshua J Coon
Mar 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yin ShenGuoping Fan
Sep 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Qianwen Sun, Dao-Xiu Zhou
Dec 3, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jeongkyung LeeJae W Lee
May 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jeongkyung LeeJae W Lee
Nov 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Scott StewartJuan Carlos Izpisua Belmonte
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Datsun A HsiaYoshihiro Izumiya
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Sebastian CanovasPablo J Ross

Citations

May 16, 1998·Human Molecular Genetics·A GreenfieldP Koopman
Apr 19, 2006·Genes & Development·Adrian P BrackenKristian Helin
Dec 19, 2006·Nature Reviews. Genetics·Yuri B Schwartz, Vincenzo Pirrotta
Dec 21, 2006·Molecular and Cellular Biology·Irina IssaevaEli Canaani
Dec 23, 2006·Development·Leonie Ringrose, Renato Paro
Jan 16, 2007·Molecular Cell·Yang Shi, Johnathan R Whetstine
Feb 27, 2007·Cell·Bernd SchuettengruberGiacomo Cavalli
Feb 27, 2007·Cell·M Azim SuraniPetra Hajkova
Mar 8, 2007·Nature Reviews. Molecular Cell Biology·R J Klose, Yi Zhang

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