title: DNA methylation variation of human-specific Alu repeats.
abstract: DNA methylation is the major repression mechanism for human retrotransposons, such as the Alu family. Here, we have determined the methylation levels associated with 5238 loci belonging to 2 Alu subfamilies, AluYa5 and AluYb8, using high-throughput targeted repeat element bisulfite sequencing (HT-TREBS). The results indicate that ∼90% of loci are repressed by high methylation levels. Of the remaining loci, many of the hypomethylated elements are found near gene promoters and show high levels of DNA methylation variation. We have characterized this variation in the context of tumorigenesis and interindividual differences. Comparison of a primary breast tumor and its matched normal tissue revealed early DNA methylation changes in ∼1% of AluYb8 elements in response to tumorigenesis. Simultaneously, AluYa5/Yb8 elements proximal to promoters also showed differences in methylation of up to one order of magnitude, even between normal individuals. Overall, the current study demonstrates that early loss of methylation occurs during tumorigenesis in a subset of young Alu elements, suggesting their potential clinical relevance. However, approaches such as deep-bisulfite-sequencing of individual loci using HT-TREBS are required to distinguish clinically relevant loci from the background observed for AluYa5/Yb8 elements in general with regard to high levels of interindividual variation in DNA methylation.
authors.affiliation: a Department of Biological Sciences , Louisiana State University , Baton Rouge , LA , USA.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Bakshi
authors.affiliation: a Department of Biological Sciences , Louisiana State University , Baton Rouge , LA , USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Herke
authors.affiliation: a Department of Biological Sciences , Louisiana State University , Baton Rouge , LA , USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Batzer
authors.affiliation: a Department of Biological Sciences , Louisiana State University , Baton Rouge , LA , USA.
authors.forename: Joomyeong
authors.initials: J
authors.lastname: Kim
mesh_terms: D020087:Alu Elements; D001943:Breast Neoplasms / Q000235:genetics*; D063646:Carcinogenesis; D002460:Cell Line; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011401:Promoter Regions, Genetic; D018626:Retroelements; D017422:Sequence Analysis, DNA; D012867:Skin / Q000166:cytology
chemical_list: D018626:Retroelements
keywords: DNA methylation; SINE; epigenetic biomarkers; epigenomes; retrotransposons