Glucocorticoid-induced alternative promoter usage for a novel 5' variant of granzyme A.
Glucocorticoids exert diverse physiological functions through transcriptional regulation of genes including granzyme A (GZMA). GZMA is one of the apoptotic effectors localized in cytotoxic T lymphocytes and is considered to mediate glucocorticoid-induced apoptosis of human leukemia 697 cells. In the present study, we identified a novel 5' variant transcript of GZMA in dexamethasone (DEX)-treated 697 cells. We designated this novel transcript as GZMAbeta. The transcription of GZMAbeta starts at 290 bp downstream of the first intronic glucocorticoid response element (GRE). Chromatin immunoprecipitation assay showed that glucocorticoid receptor (GR) binds to the intronic GRE in a DEX-dependent manner. Luciferase assay and RT-PCR also showed that DEX induces GZMAbeta transcription mediated by GR binding to the intronic GRE. Our results show that there exist at least two transcripts in human GZMA, whose expression is differentially regulated by glucocorticoid.
Ruike
Yoshinao
Y
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Katsuma
Susumu
S
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.|Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Hirasawa
Akira
A
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Tsujimoto
Gozoh
G
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan. gtsuji@pharm.kyoto-u.ac.jp.
D020121:5' Untranslated Regions / Q000235:genetics*; D017398:Alternative Splicing; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D014644:Genetic Variation; D053804:Granzymes / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008156:Luciferases; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation
D020121:5' Untranslated Regions; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D008156:Luciferases; D053804:Granzymes