Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia.

Genes & Development
Matthew G GuentherRichard A Young

Abstract

Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending across large domains. Our results define direct targets of the MLL fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in cancer.

References

Dec 4, 2001·Nature Genetics·Scott A ArmstrongStanley J Korsmeyer
Sep 14, 2002·Science·Miguel Ramalho-SantosDouglas A Melton
Jun 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·T RozovskaiaE Canaani
Nov 7, 2003·Leukemia·F ErfurthP H Domer
Apr 27, 2005·Cell·Yuki OkadaYi Zhang
May 10, 2005·Blood·Torsten HaferlachClaudia Schoch
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Matthew G GuentherRichard A Young
Aug 18, 2005·International Journal of Hematology·Mariko EguchiMel Greaves
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Thomas A MilneJay L Hess
Nov 25, 2005·British Journal of Cancer·A PuisieuxS Ansieau
Jul 25, 2006·Nature·Andrei V KrivtsovScott A Armstrong
Aug 4, 2006·Molecular Cell·B Matija Peterlin, David H Price
Aug 29, 2006·Nature Reviews. Molecular Cell Biology·Abbie SaundersJohn T Lis
Jan 16, 2007·Molecular Cell·Alexander J RuthenburgJoanna Wysocka
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
Feb 27, 2007·Cell·Bing LiJerry L Workman
Apr 28, 2007·Science·Frédéric BarabéJohn E Dick
May 25, 2007·Nature·Andrew P Feinberg
Sep 26, 2007·Human Molecular Genetics·Manel Esteller
Oct 25, 2007·Nature Reviews. Cancer·Andrei V Krivtsov, Scott A Armstrong
Feb 21, 2008·Molecular and Cellular Biology·David J StegerChristopher R Vakoc

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Citations

May 1, 2010·The Protein Journal·Geunyeong ParkJa-Eun Kim
May 11, 2010·International Journal of Hematology·Tim C P Somervaille, Michael L Cleary
Feb 16, 2010·Expert Reviews in Molecular Medicine·Constanze Bonifer, David T Bowen
Jan 14, 2010·Leukemia·C AcquavivaD Birnbaum
Mar 27, 2009·Leukemia·T Neff, S A Armstrong
Oct 6, 2012·Leukemia·O H KrämerS K Knauer
Aug 30, 2011·Nature Chemical Biology·Jon TraversPaul Workman
Sep 7, 2012·Nature Reviews. Cancer·Gabriele SulliFabrizio d'Adda di Fagagna
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kira OrlovskyEli Canaani
Jun 25, 2013·Briefings in Functional Genomics·Anthony B Mak, Jason Moffat
Dec 14, 2011·Hematology·Kathrin M Bernt, Scott A Armstrong
Dec 10, 2013·Hematology·Victoria M Richon
Feb 5, 2011·Epigenetics & Chromatin·Iris Je StulemeijerFred van Leeuwen
Jan 15, 2011·Genome Biology·Shaun MahonyDavid K Gifford
Dec 4, 2009·PLoS Biology·Dorothee MuellerRobert K Slany
Sep 17, 2010·PLoS Genetics·Michael J Guertin, John T Lis
May 27, 2014·PloS One·Wei LiuMichele Redell
May 19, 2010·Biomarkers in Medicine·Hirendra Nath Banerjee, Mukesh Verma
Dec 1, 2011·Epigenomics·Kathrin M Bernt, Scott A Armstrong
Oct 27, 2009·Future Oncology·Christian Bach, Robert K Slany
Jun 19, 2009·Haematologica·Robert K Slany
Jul 21, 2010·Journal of Visualized Experiments : JoVE·Michael L BeshiriElizaveta V Benevolenskaya
Mar 17, 2010·Expert Opinion on Therapeutic Targets·Evan R BarryTheodore P Rasmussen
Sep 11, 2012·Expert Opinion on Therapeutic Targets·James T LynchTim C P Somervaille
Apr 12, 2011·FEBS Letters·Ngai Cheung, Chi Wai Eric So
Apr 15, 2010·FEBS Letters·Joost H A Martens, Henk G Stunnenberg
Aug 8, 2012·Trends in Immunology·Aniruddha J DeshpandeScott A Armstrong
Jul 4, 2012·Leukemia Research·Oreth Montero-RuízPatricia Pérez-Vera
May 23, 2012·Experimental Hematology·Christopher R JenkinsAndrew P Weng
Jan 6, 2016·Chromosoma·Hanneke Vlaming, Fred van Leeuwen

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