Published online 15 September 2004
Nucleic Acids Research, Vol. 32 No. 16 © Oxford University Press 2004; all rights reserved
SMAR1 and Cux/CDP modulate chromatin and act as negative regulators of the TCRß enhancer (Eß)
National Center for Cell Science, Ganeshkhind, Pune 411007, India and 1 University of Texas at Austin, Molecular Genetics and Microbiology, 1, University Station A-5000, Austin, TX 78712-0162, USA
* To whom correspondence should be addressed. Tel: +91 20 2569 0922; Fax: +91 20 2569 2259; Email: samit{at}nccs.res.in
Received June 15, 2004; Revised August 3, 2004; Accepted August 17, 2004
Chromatin modulation at various cis-acting elements is critical for V(D)J recombination during T and B cell development. MARß, a matrix-associated region (MAR) located upstream of the T cell receptor ß (TCRß) enhancer (Eß), serves a crucial role in silencing Eß-mediated TCR activation. By DNaseI hypersensitivity assays, we show here that overexpression of the MAR binding proteins SMAR1 and Cux/CDP modulate the chromatin structure at MARß. We further demonstrate that the silencer function of MARß is mediated independently by SMAR1 and Cux/CDP as judged by their ability to repress Eß-dependent reporter gene expression. Moreover, the repressor activity of SMAR1 is strongly enhanced in the presence of Cux/CDP. These two proteins physically interact with each other and colocalize within the perinuclear region through a SMAR1 domain required for repression. The repression domain of SMAR1 is separate from the MARß binding domain and contains a nuclear localization signal and an arginine–serine (RS)-rich domain, characteristic of pre-mRNA splicing regulators. Our data suggest that at the double positive stage of T cell development, cis-acting MARß elements recruit the strong negative regulators Cux and SMAR1 to control Eß-mediated recombination and transcription.
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