HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 2, 948-955, January 10, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/2/948    most recent M207166200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by French, S. W. Articles by Teitell, M. A. Search for Related Content PubMed PubMed Citation Articles by French, S. W. Articles by Teitell, M. A. Social Bookmarking                      What's this?

Sp1 Transactivation of the TCL1 Oncogene^*

Samuel W. French, Cindy S. Malone^§, Rhine R. Shen, Mathilde Renard, Sarah E. Henson^§, Maurine D. Miner, Randolph Wall^§¶, and Michael A. Teitell^¶**§§

From the  Department of Pathology and Laboratory Medicine, the ^§ Department of Microbiology, Immunology, and Molecular Genetics, ^¶ Molecular Biology Institute,  Jonsson Comprehensive Cancer Center, ^** Department of Pediatrics and  AIDS Institute, David Geffen School of Medicine at UCLA, Center for the Health Sciences, Los Angeles, California 90095-1732

Cis-regions and trans-factors controlling TCL1 oncogene expression are not known. We identified the functional TCL1 promoter by mapping four transcriptional start sites 24-30 bp downstream of a TATA box. A 424-bp fragment upstream of the major start site showed robust promoter activity comparable with SV40 in both TCL1 expressing and non-expressing cell lines. Additional constructs spanning 10 kb upstream and 20 kb downstream of the start site showed only modest increases in reporter activity indicating that TCL1 expression is primarily controlled by the promoter. Ten putative Sp1-binding sites were identified within 300 bp of the start site, and three of these specifically bound Sp1. A dose-dependent transactivation of the TCL1 promoter with Sp1 addition in Sp1-negative Drosophila SL2 cells was observed, and mutation of the three identified Sp1-binding sites significantly repressed reporter gene expression in 293T cells, confirming a key role for Sp1 in activating the TCL1 promoter in vivo. In TCL1 silent cell lines, CpG DNA methylation was rarely observed at functional Sp1 sites, and methylation of a previously reported NotI restriction site was associated with dense CpG methylation rather than endogenous TCL1 gene silencing. Together, these results indicate that Sp1 mediates transactivation of the TCL1 core promoter and that TCL1 gene silencing is not dependent on mechanisms involving Sp1 and NotI site methylation.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Noguchi, V. Ropars, C. Roumestand, and F. Suizu Proto-oncogene TCL1: more than just a coactivator for Akt FASEB J, August 1, 2007; 21(10): 2273 - 2284. [Abstract] [Full Text] [PDF]

				A. I. Kuraishy, S. W. French, M. Sherman, M. Herling, D. Jones, R. Wall, and M. A. Teitell TORC2 regulates germinal center repression of the TCL1 oncoprotein to promote B cell development and inhibit transformation PNAS, June 12, 2007; 104(24): 10175 - 10180. [Abstract] [Full Text] [PDF]

				M. Hiromura, F. Suizu, M. Narita, K. Kinowaki, and M. Noguchi Identification of Nerve Growth Factor-responsive Element of the TCL1 Promoter as a Novel Negative Regulatory Element J. Biol. Chem., September 22, 2006; 281(38): 27753 - 27764. [Abstract] [Full Text] [PDF]