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

Transcriptional regulation of GSDML gene by antisense-oriented HERV-H LTR element 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

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

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Publisher
Springer Vienna
Copyright
Copyright © 2008 by Springer-Verlag
Subject
Biomedicine; Infectious Diseases; Medical Microbiology ; Virology
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-008-0105-y
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Archives of VirologySpringer Journals

Published: Jun 1, 2008

References

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