title: Enhancers in embryonic stem cells are enriched for transposable elements and genetic variations associated with cancers.
abstract: Using an enhancer-associated epigenetic signature, we made genome-wide predictions of transcriptional enhancers in human B and T lymphocytes and embryonic stem cells (ES cells). We validated and characterized the predicted enhancers using four types of information, including overlap with other genomic marks for enhancers; association with cell-type-specific genes; enrichment of cell-type-specific transcription factor binding sites; and genetic polymorphisms in predicted enhancers. We find that enhancers from ES cells, but not B or T cells, are significantly enriched for DNA sequences derived from transposable elements. This may be due to the generally relaxed repressive epigenetic state and increased activity of transposable elements in ES cells. We demonstrate that the wealth of new enhancer sequences discerned here provides an invaluable resource for the functional annotation of gene-distal single nucleotide polymorphisms identified through expression quantitative trait loci and genome-wide association studies analyses. Notably, we find GWAS SNPs associated with various cancers are enriched in ES cell enhancers. In comparison, GWAS SNPs associated with diseases due to immune dysregulation are enriched in B and T cell enhancers.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Teng
authors.forename: Hiram A
authors.initials: HA
authors.lastname: Firpi
authors.forename: Kai
authors.initials: K
authors.lastname: Tan
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites; D004251:DNA Transposable Elements; D004194:Disease / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D015870:Gene Expression; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D014157:Transcription Factors