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.
Huh
J-W
JW
Division of Biological Sciences, College of Natural Sciences, Pusan National University, Pusan 609-735, South Korea.
Kim
D-S
DS
Kang
D W
DW
Ha
H-S
HS
Ahn
K
K
Noh
Y-N
YN
Min
D S
DS
Chang
K-T
KT
Kim
H-S
HS
D001483:Base Sequence; D020077:Endogenous Retroviruses / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012190:Retroviridae / Q000235:genetics*; D020079:Terminal Repeat Sequences / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016662:Virus Integration; D000094524:Gasdermins
D009363:Neoplasm Proteins; C527978:GSDMB protein, human; D000094524:Gasdermins