The NFAT1 transcription factor is a repressor of cyclin A2 gene expression.
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.
Carvalho
Lilian D S
LD
Division of Cellular Biology, National Cancer Institute (INCA), Rio de Janeiro, Brazil.
Teixeira
Leonardo K
LK
Carrossini
Nina
N
Caldeira
Anita T N
AT
Ansel
K Mark
KM
Rao
Anjana
A
Viola
João P B
JP
D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism*; D056751:Cyclin A2; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
C508184:CCNA2 protein, mouse; D019925:Cyclin A; D056751:Cyclin A2; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; D012097:Repressor Proteins