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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 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 Citation Map 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 Müller-Tidow, C. Search for Related Content PubMed PubMed Citation Articles by Hoemme, C. Articles by Müller-Tidow, C. Related Collections Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Chromatin modifications induced by PML-RAR repress critical targets in leukemogenesis as analyzed by ChIP-Chip Claudia Hoemme1, Abdul Peerzada2, Gerhard Behre2, Yipeng Wang3, Michael McClelland3, Kay Nieselt4, Matthias Zschunke4, Christine Disselhoff1, Shuchi Agrawal1, Fabienne Isken1, Nicola Tidow1, Wolfgang E. Berdel1, Hubert Serve1, and Carsten Müller-Tidow1 1 Department of Medicine, Hematology and Oncology and Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany; 2 Department of Oncology and Hematology, University of Halle, Halle, Germany; 3 Sidney Kimmel Cancer Center, San Diego, CA; and 4 Bioinformatics Institute, University of Tübingen, Tübingen, Germany 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. Chromatin immunoprecipitation (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 trimethylation 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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