Genome-wide analysis of functional and evolutionary features of tele-enhancers

G3 (Bethesda). 2014 Apr 16;4(4):579-93. doi: 10.1534/g3.114.010447.

Abstract

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.

Keywords: enhancer; nucleotide divergence; single-nucleotide polymorphism; tissue specificity; transcription factor binding motif.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Binding Sites
  • Cell Line
  • Chromatin Immunoprecipitation
  • Enhancer Elements, Genetic*
  • Evolution, Molecular*
  • Genome, Human*
  • Humans
  • Mitochondria / metabolism
  • Myocardium / metabolism
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA
  • Support Vector Machine
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism

Substances

  • Transcription Factors