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A more recent version of this article appeared on March 15, 2002
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Papers In Press, published online ahead of print January 10, 2002
J. Biol. Chem, 10.1074/jbc.M107068200
Submitted on July 25, 2001
Revised on January 10, 2002
Accepted on January 9, 2002

Regulation of the murine NFATc1 gene by NFATc2

Bin Zhou, Randy Q. Cron, Bingruo Wu, Anna Genin, Zhili Wang, Steve Liu, Paul Robson, and H. Scott Baldwin

Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318

Corresponding Author: zhoub{at}email.chop.edu

The nuclear factors of activated T cells (NFAT) play a key role in the inducible expression of cytokine genes in T lymphocytes. NFATc1 and NFATc2 are the predominant NFAT family members in the peripheral immune system. NFATc2 is found abundantly in the cytoplasm of resting T cells, whereas NFATc1 expression is induced during T cell activation. To investigate NFATc1 regulation we characterized the structure of the murine NFATc1 gene and its 5’-flanking region. A 290-bp sequence proximal to the transcription start site was highly conserved between mouse and human, and possessed both basal and inducible promoter activity. Multiple binding sites for transcription factors were identified within this region, including a consensus NFAT-binding site. This promoter segment was cyclosporin A-sensitive and mutation of the NFAT site abrogated the inducible promoter activity as well as inhibited formation of an inducible DNA-protein complex containing NFATc2 in primary T cells. Overexpression of NFATc2 increased inducible NFATc1 promoter activity, whereas this inducibility was attenuated in NFATc2-/- splenocytes. These studies suggest that pre-existing NFATc2 contribute to the subsequent induction of NFATc1 during T cell activation.


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