Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.

TitleActivity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.
Publication TypeJournal Article
Year of Publication2018
AuthorsvonHoldt, BM, Ji, SS, Aardema, ML, Stahler, DR, Udell, MAR, Sinsheimer, JS
JournalGenome Biol Evol
Volume10
Issue6
Pagination1546-1553
Date Published2018 06 01
ISSN1759-6653
KeywordsAnimals, DNA Transposable Elements, Dogs, Epigenesis, Genetic, Gene Dosage, Gene Expression Regulation, Gene Silencing, Humans, Methylation, Transcription, Genetic, Transcriptome, Williams Syndrome, Wolves
Abstract

<p>In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions (MEIs) in dogs and Yellowstone gray wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of MEIs, suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that MEIs impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation.</p>

DOI10.1093/gbe/evy112
Alternate JournalGenome Biol Evol
PubMed ID29860323
PubMed Central IDPMC6007319
Grant ListR01 GM053275 / GM / NIGMS NIH HHS / United States