title: Placenta-restricted expression of LTR-derived NOS3.
abstract: Domestication events of long terminal repeat (LTR) sequences of the human endogenous retrovirus (HERV) family have been considered to be a new mechanism for the generation of alternative splicing in the human genome. We investigated an LTR10A belonging to the HERV-I family at the human endothelial nitric oxide synthase (NOS3) gene locus. The LTR10A element was located upstream of the original promoter sequences of NOS3. Expression analysis using RT-PCR and reporter gene assays in HCT116 and COS7 cells indicated placenta-specific expression of NOS3 driven by the LTR10A-derived promoter. The placenta-restricted expression was also determined to be associated with hypomethylation of the LTR10A element by methylation analysis using sodium bisulfite DNA sequencing. Furthermore, treatment of brain-derived cell lines with demethylation reagents did not restore expression of the LTR-derived NOS3 gene transcript. Taken together, the integration event of an LTR10A element in the upstream region of NOS3 led to the generation of a placenta-specific alternative transcript governed by cooperative mechanisms of epigenetic control (DNA methylation) and transcriptional regulation (interaction between cis- and trans-acting elements).
authors.affiliation: Division of Biological Sciences, College of Natural Sciences, Pusan National University, Changjeon-dong, Busan, Republic of Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Huh
authors.forename: H-S
authors.initials: HS
authors.lastname: Ha
authors.forename: D-S
authors.initials: DS
authors.lastname: Kim
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020079:Terminal Repeat Sequences / Q000235:genetics*; D020298:U937 Cells
chemical_list: D012333:RNA, Messenger; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III