Genome-wide Analysis of Functional and Evolutionary Features of Tele-enhancers
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Molecular Biology
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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.
Song W, Sharan R, Ovcharenko I Genome Biol. 2019; 20(1):197.
PMID: 31514731 PMC: 6739990. DOI: 10.1186/s13059-019-1808-y.
Dichotomy in redundant enhancers points to presence of initiators of gene regulation.
Song W, Ovcharenko I BMC Genomics. 2018; 19(1):947.
PMID: 30563465 PMC: 6299655. DOI: 10.1186/s12864-018-5335-0.
Identifying causal regulatory SNPs in ChIP-seq enhancers.
Huang D, Ovcharenko I Nucleic Acids Res. 2014; 43(1):225-36.
PMID: 25520196 PMC: 4288203. DOI: 10.1093/nar/gku1318.