The NFAT1 transcription factor is a repressor of cyclin A2 gene expression

Cell Cycle. 2007 Jul 15;6(14):1789-95. doi: 10.4161/cc.6.14.4473. Epub 2007 May 21.

Abstract

The NFAT (Nuclear Factor of Activated T cells) family of transcription factors plays a central role in the regulation of several genes related to the immune response. Recently, NFAT proteins have been implicated in the proliferation and differentiation of different cell types. Previous studies have shown that NFAT1-deficient mice display lymphocyte hyperproliferation, shortened cell cycle duration, and cyclin overexpression. Here, we demonstrate that cyclin A2 expression is upregulated in the absence of NFAT1 in lymphocytes. Ectopic expression of NFAT1 in CHO cells decreases cyclin A2 levels. Indeed, NFAT1 binds to a consensus binding site found at the mouse cyclin A2 promoter in vitro and in vivo. Luciferase reporter assays show that NFAT1 downregulates cyclin A2 expression by directly binding to the cyclin A2 promoter. Together, these results indicate that the NFAT1 transcription factor represses cyclin A2 expression in lymphocytes, and may act as a silencer of gene transcription during the cell cycle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Cycle / physiology
  • Cricetinae
  • Cricetulus
  • Cyclin A / genetics
  • Cyclin A / metabolism*
  • Cyclin A2
  • Gene Expression Regulation*
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / physiology*
  • Mice
  • Mice, Knockout
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • Promoter Regions, Genetic
  • Regulatory Elements, Transcriptional
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • CCNA2 protein, mouse
  • Cyclin A
  • Cyclin A2
  • NFATC Transcription Factors
  • Nfatc2 protein, mouse
  • Repressor Proteins