Regulation of the murine Nfatc1 gene by NFATc2

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

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

NFAT proteins 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 is highly conserved between mouse and human and possesses both basal and inducible promoter activities. 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 inducible promoter activity and 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. This study suggests that pre-existing NFATc2 contributes to the subsequent induction of Nfatc1 during T cell activation.

Original languageEnglish (US)
Pages (from-to)10704-10711
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number12
DOIs
StatePublished - Mar 22 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Zhou, B., Cron, R. Q., Wu, B., Genin, A., Wang, Z., Liu, S., Robson, P., & Scott Baldwin, H. (2002). Regulation of the murine Nfatc1 gene by NFATc2. Journal of Biological Chemistry, 277(12), 10704-10711. https://doi.org/10.1074/jbc.M107068200