Genome-wide analysis of functional and evolutionary features of tele-enhancers.
We investigated sequence features of enhancers separated from their target gene by at least one intermediate gene/exon (named tele-enhancers in this study) and enhancers residing inside their target gene locus. In this study, we used whole genome enhancer maps and gene expression profiles to establish a large panel of tele-enhancers. By contrasting tele-enhancers to proximal enhancers targeting heart genes, we observed that heart tele-enhancers use unique regulatory mechanisms based on the cardiac transcription factors SRF, TEAD, and NKX-2.5, whereas proximal heart enhancers rely on GATA4 instead. A functional analysis showed that tele-enhancers preferentially regulate house-keeping genes and genes with a metabolic role during heart development. In addition, tele-enhancers are significantly more conserved than their proximal counterparts. Similar trends have been observed for non-heart tissues and cell types, suggesting that our findings represent general characteristics of tele-enhancers.
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892.
Di
D
Huang
Ivan
I
Ovcharenko
D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D060388:Support Vector Machine; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
D014157:Transcription Factors
enhancer; nucleotide divergence; single-nucleotide polymorphism; tissue specificity; transcription factor binding motif