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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4445-4454. Prepublished online as a Blood First Edition Paper on September 12, 2007; DOI 10.1182/blood-2007-05-090514. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-090514v1 110/13/4445    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 Mueller, D. Articles by Slany, R. K. Search for Related Content PubMed PubMed Citation Articles by Mueller, D. Articles by Slany, R. K. Related Collections Neoplasia Oncogenes and Tumor Suppressors Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification Dorothee Mueller1, Christian Bach1, Deniz Zeisig1, Maria-Paz Garcia-Cuellar1,3, Sara Monroe2, Arun Sreekumar2, Rong Zhou2, Alexey Nesvizhskii2, Arul Chinnaiyan2, Jay L. Hess2, and Robert K. Slany1 1 Department of Genetics, University Erlangen, Erlangen, Germany; 2 Department of Pathology, University of Michigan Medical School, Ann Arbor; and 3 Department of Hematology and Oncology, Dr. von Haunersches Kinderspital, Munich, Germany Chimeric proteins joining the histone methyltransferase MLL with various fusion partners trigger distinctive lymphoid and myeloid leukemias. Here, we immunopurified proteins associated with ENL, a protein commonly fused to MLL. Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR). The composition of EAP was further verified by coimmunoprecipitation, 2-hybrid analysis, pull-down, and colocalization experiments. Purified EAP showed a histone H3 lysine 79–specific methylase activity, displayed a robust RNAPolII CTD kinase function, and counteracted the effect of the pTEFb inhibitor 5,6-dichloro-benzimidazole-riboside. In vivo, an ENL knock-down diminished genome-wide as well as gene-specific H3K79 dimethylation, reduced global run-on elongation, and inhibited transient transcriptional reporter activity. According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. G. Muntean and J. L. Hess Epigenetic Dysregulation in Cancer Am. J. Pathol., October 1, 2009; 175(4): 1353 - 1361. [Abstract] [Full Text] [PDF] R. K. Slany The molecular biology of mixed lineage leukemia Haematologica, July 1, 2009; 94(7): 984 - 993. [Abstract] [Full Text] [PDF] J. Kohoutek, Q. Li, D. Blazek, Z. Luo, H. Jiang, and B. M. Peterlin Cyclin T2 Is Essential for Mouse Embryogenesis Mol. Cell. Biol., June 15, 2009; 29(12): 3280 - 3285. [Abstract] [Full Text] [PDF] M. Liedtke and M. L. Cleary Therapeutic targeting of MLL Blood, June 11, 2009; 113(24): 6061 - 6068. [Abstract] [Full Text] [PDF] R. Popovic, L. E. Riesbeck, C. S. 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