Abstract
BackgroundRetrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability.Methodswe examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation.ResultsWe observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression.ConclusionThe mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.
Highlights
Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution
Screening of AluYa5 insertional polymorphisms in cell lines To find insertional polymorphic retrotransposons, we screened Raji, Jurkat, HT15, H1299, MCF, and K562 cell lines using the primer sets listed in the Methods section
The primers flanked the newly inserted retrotransposon AluYa5 in chr11:100,911,358-100,912,065 locus (Assembly: hg19), presence of Alu insertion could be distinguished by length of PCR amplicon
Summary
Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. According to the 2001 analysis, which has been confirmed overall by the 2004 update (International Human Genome Sequencing Consortium 2004), short interspersed elements (SINEs), such as Alu or SINE-R/VNTR/Alu (SVA), account for 13%, Long interspersed elements [LINE-1(L1)] for 20%, and long-terminal repeat (LTR) retrotransposons, such as endogenous retrovirus (ERV), for 8%, respectively, of the sequenced human genome The retrotransposons increase their copy number by retrotransposition via RNA. It is estimated that there is one Alu retrotransposon insertion every 21 births [5] during gametogenesis, transferring the retrotransposon’s genetic information to the generation [6,7] These retrotransposition events are likely to change the activity of genes at the insertion site, including increased or decreased transcriptional activity.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
