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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1392-1401. Prepublished online as a Blood First Edition Paper on May 29, 2008; DOI 10.1182/blood-2007-11-124735. This Article Full Text Full Text (PDF) Supplemental Methods, Table, and Figures All Versions of this Article: blood-2007-11-124735v1 112/4/1392    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 Okumura, A. J. Articles by Zhang, D.-E. Search for Related Content PubMed PubMed Citation Articles by Okumura, A. J. Articles by Zhang, D.-E. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA t(8;21)(q22;q22) fusion proteins preferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate gene expression Akiko J. Okumura1,2, Luke F. Peterson1, Fumihiko Okumura1, Anita Boyapati1, and Dong-Er Zhang13 1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; and 2 Moores UCSD Cancer Center and 3 Department of Pathology and Division of Biological Sciences, University of California San Diego, La Jolla Chromosome abnormalities are frequently associated with cancer development. The 8;21(q22;q22) chromosomal translocation is one of the most common chromosome abnormalities identified in leukemia. It generates fusion proteins between AML1 and ETO. Since AML1 is a well-defined DNA-binding protein, AML1-ETO fusion proteins have been recognized as DNA-binding proteins interacting with the same consensus DNA-binding site as AML1. The alteration of AML1 target gene expression due to the presence of AML1-ETO is related to the development of leukemia. Here, using a 25-bp random double-stranded oligonucleotide library and a polymerase chain reaction (PCR)-based DNA-binding site screen, we show that compared with native AML1, AML1-ETO fusion proteins preferentially bind to DNA sequences with duplicated AML1 consensus sites. This finding is further confirmed by both in vitro and in vivo DNA-protein interaction assays. These results suggest that AML1-ETO fusion proteins have a selective preference for certain AML1 target genes that contain multimerized AML1 consensus sites in their regulatory elements. Such selected regulation provides an important molecular mechanism for the dysregulation of gene expression during cancer development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Yan, E.-Y. Ahn, S. W. Hiebert, and D.-E. Zhang RUNX1/AML1 DNA-binding domain and ETO/MTG8 NHR2-dimerization domain are critical to AML1-ETO9a leukemogenesis Blood, January 22, 2009; 113(4): 883 - 886. [Abstract] [Full Text] [PDF]

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