title: The transcriptional activity of HERV-I LTR is negatively regulated by its cis-elements and wild type p53 tumor suppressor protein.
abstract: Human endogenous retroviruses (HERVs), abundantly inter-dispersed in the genome, carry long terminal repeats (LTRs) that may potentially retro-transpose to new genomic sites and deregulate the neighboring cellular genes. However, normally HERVs are either structurally defective or inactive due possibly to stringent negative control mechanisms. To study the possible negative regulation of HERV, we isolated the LTR of RTVL-Ia and constructed site-specific mutations for analysis of the promoter and enhancer functions by using chloramphenicol acetyl transferase (CAT) reporter assay. Our results showed that in most transfected human cells the LTR-mediated CAT expression was negligible unless a sequence segment at the AGTAAA polyadenylation site was deleted. In addition, we have found that the wild type p53 may inhibit whereas a p53 mutant (V143A) stimulate the transcriptional activity of HERV-I LTR. Our results imply that HERV-I LTR, while under negative control by its LTR cis-elements and by wild type p53, may become active upon p53 mutation.
authors.affiliation: Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Nien-Tzu
authors.initials: NT
authors.lastname: Chang
authors.forename: Wen K
authors.initials: WK
authors.lastname: Yang
authors.forename: Huey-Chung
authors.initials: HC
authors.lastname: Huang
authors.forename: Kai-Wun
authors.initials: KW
authors.lastname: Yeh
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Wu
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase