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

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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

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T-cells
Genes
T-Lymphocytes
Chemical activation
Binding Sites
NFATC Transcription Factors
5' Flanking Region
Immune system
Transcription Initiation Site
Cyclosporine
Immune System
Consensus
Cytoplasm
Transcription Factors
Cytokines
Gene Expression
Mutation
DNA
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Zhou, B., Cron, R. Q., Wu, B., Genin, A., Wang, Z., Liu, S., ... 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

Regulation of the murine Nfatc1 gene by NFATc2. / Zhou, Bin; Cron, Randy Q.; Wu, Bingruo; Genin, Anna; Wang, Zhili; Liu, Steve; Robson, Paul; Scott Baldwin, H.

In: Journal of Biological Chemistry, Vol. 277, No. 12, 22.03.2002, p. 10704-10711.

Research output: Contribution to journalArticle

Zhou, B, Cron, RQ, 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, vol. 277, no. 12, pp. 10704-10711. https://doi.org/10.1074/jbc.M107068200
Zhou, Bin ; Cron, Randy Q. ; Wu, Bingruo ; Genin, Anna ; Wang, Zhili ; Liu, Steve ; Robson, Paul ; Scott Baldwin, H. / Regulation of the murine Nfatc1 gene by NFATc2. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 12. pp. 10704-10711.
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AU - Robson, Paul

AU - Scott Baldwin, H.

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