Identification of human granzyme B promoter regulatory elements interacting with activated T-cell-specific proteins: implication of Ikaros and CBF binding sites in promoter activation.
Granzyme B serine protease is found in the granules of activated cytotoxic T cells and in natural and lymphokine-activated killer cells. This protease plays a critical role in the rapid induction of target cell DNA fragmentation. The DNA regulatory elements that are responsible for the specificity of granzyme B gene transcription in activated T-cells reside between nt -148 and +60 (relative to the transcription start point at +1) of the human granzyme B gene promoter. This region contains binding sites for the transcription factors Ikaros, CBF, Ets, and AP-1. Mutational analysis of the human granzyme B promoter reveals that the Ikaros binding site (-143 to -114) and the AP-1/CBF binding site (-103 to -77) are essential for the activation of transcription in phytohemagglutinin-activated peripheral blood lymphocytes, whereas mutation of the Ets binding site does not affect promoter activity in these cells.
Wargnier
A
A
Institut National de la Santé et de la Recherche Médicale U93, Centre Hayem, Hôpital St. Louis, Paris, France.
Legros-Maida
S
S
Bosselut
R
R
Bourge
J F
JF
Lafaurie
C
C
Ghysdael
C J
CJ
Sasportes
M
M
Paul
P
P
D001483:Base Sequence; D001665:Binding Sites; D050660:Core Binding Factors; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D053804:Granzymes; D006801:Humans; D051740:Ikaros Transcription Factor; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D050660:Core Binding Factors; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases