Abstract
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 GZMAβ. The transcription of GZMAβ 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 GZMAβ 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.
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Acknowledgments
We thank Professor Shigeaki Kato (University of Tokyo) for providing the expression plasmid for GR. This work was supported in part by research grants from the ScientificFund of the Ministry of Education, Science, and Culture of Japan (to G.T.); the Japan Health Science Foundation and the Ministry of Human Health and Welfare (to G.T.); and the 21st Century Center of Excellence Program “Knowledge Information Infrastructure for Genome Science” (to G.T., S.K. and Y.R.).
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The cDNA sequence of a novel 5′ variant of granzyme A (designated as granzyme Aβ; GZMAβ) was deposited in GeneBank under number AB284134.
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Ruike, Y., Katsuma, S., Hirasawa, A. et al. Glucocorticoid-induced alternative promoter usage for a novel 5′ variant of granzyme A. J Hum Genet 52, 172–178 (2007). https://doi.org/10.1007/s10038-006-0099-9
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DOI: https://doi.org/10.1007/s10038-006-0099-9
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