SMAR1 and Cux/CDP modulate chromatin and act as negative regulators of the TCRbeta enhancer (Ebeta)

Nucleic Acids Research
Ruchika Kaul-GhanekarSamit Chattopadhyay

Abstract

Chromatin modulation at various cis-acting elements is critical for V(D)J recombination during T and B cell development. MARbeta, a matrix-associated region (MAR) located upstream of the T cell receptor beta (TCRbeta) enhancer (Ebeta), serves a crucial role in silencing Ebeta-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 MARbeta. We further demonstrate that the silencer function of MARbeta is mediated independently by SMAR1 and Cux/CDP as judged by their ability to repress Ebeta-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 MARbeta 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 MARbeta elements recruit the strong negative regulators Cux and SMA...Continue Reading

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Citations

Jan 22, 2008·Bioinformatics·Saraswathi AbhimanL Aravind
Sep 17, 2005·Molecular and Cellular Biology·Shravanti RampalliSamit Chattopadhyay
Sep 18, 2012·BMC Molecular Biology·Sandeep SinghSamit Chattopadhyay
Mar 29, 2014·International Journal of Molecular Medicine·Dariusz GrzankaMagdalena Izdebska
Aug 17, 2010·Biochimica Et Biophysica Acta·Sunil Kumar MaloniaSamit Chattopadhyay
Dec 17, 2009·Biochemical and Biophysical Research Communications·Kamini SinghSamit Chattopadhyay
Mar 4, 2008·Gene·Laurent Sansregret, Alain Nepveu
Feb 2, 2006·Immunological Reviews·Michele K Anderson
Feb 2, 2006·Immunological Reviews·Annette M Jackson, Michael S Krangel
Nov 27, 2015·The Indian Journal of Medical Research·Bhalchandra MirlekarSamit Chattopadhyay
Feb 11, 2005·The Journal of Biological Chemistry·Archana JalotaSamit Chattopadhyay
Feb 23, 2010·Molecular Biology Reports·Tian-Yun WangJun-He Zhang
Dec 15, 2019·Nature Communications·Malin UeberschärQi Dai
Oct 6, 2009·Molecular and Cellular Biochemistry·Kiran K Nakka, Samit Chattopadhyay
Feb 25, 2017·Frontiers in Immunology·Bhalchandra MirlekarSamit Chattopadhyay
Dec 30, 2004·The Journal of Biological Chemistry·Ruchika Kaul-GhanekarSamit Chattopadhyay

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