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 SMAR1 to control Ebeta-mediated recombination and transcription.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Kaul-Ghanekar R,Jalota A,Pavithra L,Tucker P,Chattopadhyay Sdoi
10.1093/nar/gkh807keywords:
subject
Has Abstractpub_date
2004-09-15 00:00:00pages
4862-75issue
16eissn
0305-1048issn
1362-4962pii
32/16/4862journal_volume
32pub_type
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