Placenta-restricted expression of LTR-derived NOS3

Placenta. 2008 Jul;29(7):602-8. doi: 10.1016/j.placenta.2008.04.002. Epub 2008 May 13.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Epigenesis, Genetic / physiology
  • Female
  • HCT116 Cells
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Insertional / physiology
  • Nitric Oxide Synthase Type III / genetics*
  • Nitric Oxide Synthase Type III / metabolism
  • Organ Specificity / genetics
  • Placenta / metabolism*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Terminal Repeat Sequences / genetics*
  • U937 Cells

Substances

  • RNA, Messenger
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III