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Nat Genet. 2017 Jul;49(7):1073-1081. doi: 10.1038/ng.3884. Epub 2017 Jun 5.

Genome-wide characterization of mammalian promoters with distal enhancer functions.

Author information

1
Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.
2
INSERM, UMR 967, CEA/DRF/iRCM, Laboratory of Molecular Hematopoiesis, Université Paris-Diderot, Université Paris-Saclay, Fontenay-aux-Roses, France.
3
Labex GR-Ex, Université Sorbonne Paris Cité, Paris, France.
4
IGMM, CNRS, Université de Montpellier, Montpellier, France.
5
Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Juriquilla, Mexico.

Abstract

Gene expression in mammals is precisely regulated by the combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might have enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease.

PMID:
28581502
DOI:
10.1038/ng.3884
[Indexed for MEDLINE]

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