TY - JOUR
T1 - Activity of genes with functions in human Williams-Beuren syndrome is impacted by mobile element insertions in the gray wolf genome
AU - VonHoldt, Bridgett M.
AU - Ji, Sarah S.
AU - Aardema, Matthew L.
AU - Stahler, Daniel R.
AU - Udell, Monique A.R.
AU - Sinsheimer, Janet S.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - In canines, transposon dynamics have been associatedwith 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 associatedwith 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.
AB - In canines, transposon dynamics have been associatedwith 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 associatedwith 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.
KW - Canines
KW - Expression
KW - Hypersociability
KW - Methylation
KW - Transposons
UR - http://www.scopus.com/inward/record.url?scp=85051999884&partnerID=8YFLogxK
U2 - 10.1093/gbe/evy112
DO - 10.1093/gbe/evy112
M3 - Article
C2 - 29860323
AN - SCOPUS:85051999884
SN - 1759-6653
VL - 10
SP - 1546
EP - 1553
JO - Genome Biology and Evolution
JF - Genome Biology and Evolution
IS - 6
ER -