Abstract
The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominent in actively transcribed regions of the genome; however, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 and a member of the Jumonji C family of proteins known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via occupancy of promoters and demethylation of H3K79. Furthermore, genome-wide analysis suggests that H3K79 methylation levels increase when KDM2B is depleted, which indicates that KDM2B functions as an H3K79 demethylase in vivo. Finally, stable KDM2B-knockdown cell lines exhibit displacement of NAD+-dependent deacetylase sirtuin-1 (SIRT1) from chromatin, with concomitant increases in H3K79 methylation and H4K16 acetylation. Our findings identify KDM2B as an H3K79 demethylase and link its function to transcriptional repression via SIRT1-mediated chromatin silencing.-Kang, J.-Y., Kim, J.-Y., Kim, K.-B., Park, J. W., Cho, H., Hahm, J. Y., Chae, Y.-C., Kim, D., Kook, H., Rhee, S., Ha, N.-C., Seo, S.-B. KDM2B is a histone H3K79 demethylase and induces tran...Continue Reading
References
Sep 26, 1997·Nature·K LugerT J Richmond
Jan 19, 2000·Nature·B D Strahl, C D Allis
Oct 20, 2000·Analytical Biochemistry·J M LizcanoK F Tipton
Nov 1, 2000·Cell·P CheungP Sassone-Corsi
Jun 25, 2002·Genes & Development·Huck Hui NgKevin Struhl
Jun 28, 2002·Cell·Fred van LeeuwenDaniel E Gottschling
Jul 5, 2002·The Journal of Biological Chemistry·Nicolas LacosteJacques Côte
Jul 19, 2002·Current Biology : CB·Qin FengYi Zhang
Aug 2, 2002·Nature·Scott D BriggsBrian D Strahl
Aug 9, 2002·The Journal of Biological Chemistry·Huck Hui NgKevin Struhl
Feb 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Huck Hui NgKevin Struhl
Feb 27, 2003·The Journal of Biological Chemistry·Hogune ImEmery H Bresnick
Jun 4, 2004·Genes & Development·Dirk SchübelerMark Groudine
Sep 17, 2004·Genetics·Gregory A ShanowerPaul Schedl
Oct 8, 2004·Molecular Cell·Alejandro VaqueroDanny Reinberg
Nov 5, 2004·Nature·Yentram HuyenThanos D Halazonetis
Dec 29, 2004·Cell·Yujiang ShiYang Shi
Apr 27, 2005·Cell·Yuki OkadaYi Zhang
Aug 25, 2005·Cold Spring Harbor Symposia on Quantitative Biology·C B MillarM Grunstein
Aug 27, 2005·Cell·Dmitry K PokholokRichard A Young
Sep 7, 2005·Cell·Joanna WysockaC David Allis
Sep 17, 2005·Molecular and Cellular Biology·Robert WysockiStephen J Kron
Nov 2, 2005·Nature Reviews. Molecular Cell Biology·Cyrus Martin, Yi Zhang
Dec 20, 2005·Nature·Yu-ichi TsukadaYi Zhang
Apr 19, 2006·Genes & Development·Adrian P BrackenKristian Helin
May 23, 2006·Nucleic Acids Research·Erica L Mersfelder, Mark R Parthun
Aug 22, 2006·Nature Cell Biology·Yuki OkadaYi Zhang
Oct 13, 2006·Molecular and Cellular Biology·Christopher R VakocGerd A Blobel
Dec 1, 2006·Human Molecular Genetics·Emmanuelle BitounKay E Davies
Feb 14, 2007·Molecular & Cellular Proteomics : MCP·Carmen SánchezMiguel Vidal
Mar 14, 2007·Cell·Matthew D SimonKevan M Shokat
May 25, 2007·Nature·Shelley L Berger
Aug 24, 2007·Nature·Karl AggerKristian Helin
Sep 15, 2007·Blood·Dorothee MuellerRobert K Slany
Nov 13, 2007·Nature·David FrescasMichele Pagano
Nov 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sunhwa HongKai Ge
Nov 16, 2007·Biology of Reproduction·Masatoshi OogaFugaku Aoki
Dec 27, 2007·Molecular Cell·Mohammed AltafJacques Côté
Feb 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Raymond PfauPhilip N Tsichlis
Feb 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alexandros TzatsosPhilip N Tsichlis
Aug 18, 2009·Molecular Cell·Julia M SchulzeAli Shilatifard
Apr 9, 2010·Annual Review of Biochemistry·Nima Mosammaparast, Yang Shi
Apr 27, 2010·Molecular Cell·Neil P BlackledgeRobert J Klose
Sep 4, 2010·Cell·Jung-Shin LeeAli Shilatifard
Jan 18, 2011·The Journal of Biological Chemistry·Wen YuanBing Zhu
Feb 12, 2011·Blood·Jin HeYi Zhang
May 21, 2011·Molecular Cell·Tineke L LenstraFrank C P Holstege
Jul 5, 2011·Genes & Development·Anh Tram Nguyen, Yi Zhang
Jul 12, 2011·Cancer Cell·Kathrin M BerntScott A Armstrong
Nov 19, 2011·Cancer Cell·Jiaying TanJay L Hess
Citations
Jul 31, 2018·Nucleus·Tomáš VacíkIvan Raška
Feb 14, 2019·Expert Opinion on Therapeutic Targets·Tyler S McCannPaul Jedlicka
Jan 11, 2020·PLoS Pathogens·Nenavath Gopal NaikZsolt Toth
Feb 6, 2020·Briefings in Bioinformatics·Jie WuChaohan Xu
Dec 6, 2019·Frontiers in Pediatrics·Annalisa LonettiRiccardo Masetti
Apr 26, 2019·Archives of Pharmacal Research·Ja-Eun Kim
Jul 28, 2020·PloS One·Hyeonsoo Jung, Sang-Beom Seo
Oct 9, 2020·Cell Proliferation·Joo-Young KangSang-Beom Seo
Oct 28, 2020·ELife·Danielle YiHei Sook Sul
Apr 10, 2020·The Protein Journal·Eleftherios E DeiktakisSotirios C Kampranis
Jan 16, 2021·Cancer Letters·Yangyang YangHuijian Wu
Feb 11, 2021·Experimental & Molecular Medicine·Duk-Hwa KwonHyun Kook
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Guo LiWei-Guo Zhu
Nov 26, 2018·Molecular Cell·Emma J ChoryGerald R Crabtree
Mar 16, 2019·Current Opinion in Chemical Biology·Tatsiana KosciukHening Lin
Mar 26, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Beatriz Maria Veloso PereiraKarina Thieme
Mar 30, 2021·The Journal of Biological Chemistry·Sasithorn Wanna-UdomTakeshi Suzuki
Apr 4, 2021·International Journal of Molecular Sciences·Oriol de Barrios, Maribel Parra
Apr 17, 2021·Frontiers in Genetics·Elena Di NisioRodolfo Negri
May 1, 2021·Viruses·Natalie AtyeoZsolt Toth
Mar 12, 2021·Journal of Virology·Nenavath Gopal NaikZsolt Toth
May 27, 2021·The Journal of Cell Biology·Kelly E LeonKatherine M Aird
Jun 25, 2021·World Journal of Gastroenterology : WJG·Prashika SinghKristie Bloom
Dec 23, 2021·Immunological Reviews·Atsushi OnoderaToshinori Nakayama