title: (Some) cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1.
abstract: DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs) is not well investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza-dC, results in significantly increased levels of HERV-Fc1 expression in cells previously not expressing HERV-Fc1, or with a very low expression level. The extent of expression of HERV-Fc1 RNAs precisely correlates with the apparent extent of demethylation of the related DNA sequences. In conclusion, the results suggest that inhibition of DNA methylation/histone deacetylase can interfere with gene silencing mechanisms affecting HERV-Fc1 expression in human cells.
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark. laska@hum-gen.au.dk
authors: Magdalena Janina
authors: MJ
authors: Laska
authors: Kari Konstantin
authors: KK
authors: Nissen
authors: Bjørn Andersen
authors: BA
authors: Nexø
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000077209:Decitabine; D020077:Endogenous Retroviruses / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D018626:Retroelements / Q000235:genetics*; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic
chemical_list: D006877:Hydroxamic Acids; D018626:Retroelements; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine
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