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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2753-2760. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-07-2482. This Article Full Text (PDF) All Versions of this Article: 2003-07-2482v1 103/7/2753    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 Yoshida, M. Articles by Matsuoka, M. Search for Related Content PubMed PubMed Citation Articles by Yoshida, M. Articles by Matsuoka, M. Social Bookmarking                   What's this? Submitted July 23, 2003 Accepted November 17, 2003 Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells Mika Yoshida, Kisato Nosaka, Jun-ichirou Yasunaga, Ichiro Nishikata, Kazuhiro Morishita, and Masao Matsuoka* Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan Department of Biochemistry, Medical College, University of Miyazaki, Miyazaki, Japan * Corresponding author; email: mmatsuok{at}virus.kyoto-u.ac.jp. DNA methylation plays critical roles in the development and differentiation of mammalian cells, and its dysregulation has been implicated in oncogenesis. This study was designed to determine whether DNA hypomethylation-associated aberrant gene expression is involved in ATL leukemogenesis. We isolated hypomethylated DNA regions of ATL cells compared with peripheral blood mononuclear cells from a carrier by a methylated CpG-island amplification/representational difference analysis method. The DNA regions identified contained MEL1, CACNA1H and Nogo receptor genes. Sequencing using sodium bisulfite-treated genomic DNAs revealed the decreased methylated-CpG sites, confirming that this method detected hypomethylated DNA regions. Moreover, these hypomethylated genes were aberrantly transcribed. Among them, MEL1S, an alternatively spliced form of MEL1 lacking the PR (PRDI-BF1 and RIZ1) domain, was frequently transcribed in ATL cells, and the transcriptional initiation sites were identified upstream from exon 4 and 6. Transfection of MEL1S into CTLL-2 cells conferred resistance against TGF-, suggesting that aberrant expression of MEL1S was associated with dysregulation of TGF--mediated signaling. Although Tax renders cells resistant to TGF-, Tax could not be produced in most fresh ATL cells, in which MEL1S might be responsible for TGF- resistance. Our results suggest that aberrant gene expression associated with DNA hypomethylation is implicated in the leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Seale, S. Kajimura, and B. M. Spiegelman Transcriptional control of brown adipocyte development and physiological function--of mice and men Genes & Dev., April 1, 2009; 23(7): 788 - 797. [Abstract] [Full Text] [PDF] M. Takahata, Y. Inoue, H. Tsuda, I. Imoto, D. Koinuma, M. Hayashi, T. Ichikura, T. Yamori, K. Nagasaki, M. Yoshida, et al. SKI and MEL1 Cooperate to Inhibit Transforming Growth Factor-{beta} Signal in Gastric Cancer Cells J. Biol. Chem., January 30, 2009; 284(5): 3334 - 3344. [Abstract] [Full Text] [PDF] T. Hidaka, S. Nakahata, K. Hatakeyama, M. Hamasaki, K. 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