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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2887-2895. Prepublished online as a Blood First Edition Paper on November 16, 2007; DOI 10.1182/blood-2007-03-079921. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2007-03-079921v1 111/5/2887    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hoemme, C. Articles by Muller-Tidow, C. Search for Related Content PubMed PubMed Citation Articles by Hoemme, C. Articles by Muller-Tidow, C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 15, 2007 Accepted November 5, 2007 Chromatin modifications induced by PML-RAR repress critical targets in leukemogenesis as analyzed by ChIP-Chip Claudia Hoemme, Abdul Peerzada, Gerhard Behre, Yipeng Wang, Michael McClelland, Kay Nieselt, Matthias Zschunke, Christine Disselhoff, Shuchi Agrawal, Fabienne Isken, Nicola Tidow, Wolfgang E. Berdel, Hubert Serve, and Carsten Muller-Tidow* Department of Medicine, Hematology and Oncology, and Interdisciplinary Center for Clinical Research (IZKF), University of Munster, Munster, Germany Department of Oncology and Hematology, University of Halle, Halle, Germany Sidney Kimmel Cancer Center, San Diego, CA, United States Bioinformatics Institute, University of Tubingen, Tubingen, Germany * Corresponding author; email: muellerc{at}uni-muenster.de. The translocation t(15;17) generates the chimeric PML-RAR transcription factor that is the initiating event of acute promyelocytic leukemia. A global view of PML-RAR transcriptional functions was obtained by genome-wide binding and chromatin modification analyses, combined with genome wide expression data. ChIP-chip experiments identified 372 direct genomic PML-RAR targets. A subset of these was confirmed in primary acute promyelocytic leukemia. Direct PML-RAR targets include regulators of global transcriptional programs as well as critical regulatory genes for basic cellular functions such as cell cycle control and apoptosis. PML-RAR binding universally led to HDAC1 recruitment, loss of histone H3 acetylation, increased tri-methylation of histone H3 lysine 9 and unexpectedly increased tri-methylation of histone H3 lysine 4. The binding of PML-RAR to target promoters and the resulting histone modifications resulted in mRNA repression of functionally relevant genes. Taken together our results reveal that the transcription factor PML-RAR regulates key cancer related genes and pathways by inducing a repressed chromatin formation on its direct genomic target genes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Epigenomic repression by APL oncoprotein Filippa Pettersson and Wilson H. Miller, Jr Blood 2008 111: 2498. [Full Text] [PDF] This article has been cited by other articles: G. H. S. Richter, S. Plehm, A. Fasan, S. Rossler, R. Unland, I. M. Bennani-Baiti, M. Hotfilder, D. Lowel, I. von Luettichau, I. Mossbrugger, et al. EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation PNAS, March 31, 2009; 106(13): 5324 - 5329. [Abstract] [Full Text] [PDF] B. Hackanson, H. Becker, T. Berg, M. Binder, C. Dierks, J. Duque-Afonso, M. D. Lairmore, H. S. Schafer, M. Schnitzler, R. Zeiser, et al. XXIII International Association for Comparative Research on Leukemia and Related Diseases Symposium: from Molecular Pathogenesis to Targeted Therapy in Leukemia and Solid Tumors Cancer Res., July 15, 2008; 68(14): 5512 - 5518. [Full Text] [PDF]

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