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Arch Virol. 2008;153(6):1201-5. doi: 10.1007/s00705-008-0105-y. Epub 2008 May 14.

Transcriptional regulation of GSDML gene by antisense-oriented HERV-H LTR element.

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Division of Biological Sciences, College of Natural Sciences, Pusan National University, Pusan 609-735, South Korea.


During the course of hominoid evolution, a new transcript variant of the GSDML (gasdermin-like protein) gene was formed by the integration of the antisense-oriented HERV-H (human endogenous retrovirus) LTR (long terminal repeat) element. To investigate regions that are critical for transcriptional regulation of the GSDML gene, we generated seven deletion mutants from a full-length clone (clone 1/630) that includes the HERV-H LTR sequence and compared their expression levels relative to the full-length parental clone using a transient transfection assay. In the transient transfection assay, deletion of the 5' flanking region (cellular origin) of the HERV-H LTR sequence led to a 4.5-fold increase in expression compared to the full-length clone, while deletion of the U5 region showed a significant decrease in transcriptional activity. Deletion of the 3' flanking region of the LTR sequence (clone 42/451) showed similar transcriptional activity to a clone missing the 5' flanking region of cellular origin (clone 42/630). Taken together, these data indicate that the HERV-H LTR sequence (viral origin) positively regulates transcriptional activity of the GSDML gene and that the 5' flanking region sequence (cellular origin) exerts negative transcriptional regulation.

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