Genome-wide characterization of mammalian promoters with distal enhancer functions

被引：185

作者：

Dao, Lan T. M. ^{[1
,6
]}

Galindo-Albarran, Ariel O. ^{[1
]}

Castro-Mondragon, Jaime A. ^{[1
]}

Andrieu-Soler, Charlotte ^{[3
,4
]}

Medina-Rivera, Alejandra ^{[5
]}

Souaid, Charbel ^{[1
,2
]}

Charbonnier, Guillaume ^{[1
]}

Griffon, Aurelien ^{[1
]}

Vanhille, Laurent ^{[1
]}

Stephen, Tharshana ^{[2
,4
]}

Alomairi, Jaafar ^{[1
]}

Martin, David ^{[4
]}

Torres, Magali ^{[1
]}

Fernandez, Nicolas ^{[1
]}

Soler, Eric ^{[2
,3
,4
]}

van Helden, Jacques ^{[1
]}

Puthier, Denis ^{[1
]}

Spicuglia, Salvatore ^{[1
]}

机构：

[1] Aix Marseille Univ, INSERM, TAGC, UMR 1090, Marseille, France

[2] Univ Paris Saclay, Univ Paris Diderot, Lab Mol Hematopoiesis, INSERM,UMR 967,CEA,DRF,iRCM, Fontenay Aux Roses, France

[3] Univ Sorbonne Paris Cite, Labex GR Ex, Paris, France

[4] Univ Montpellier, IGMM, CNRS, Montpellier, France

[5] Univ Nacl Autonoma Mexico, Lab Int Invest Genoma Humano, Juriquilla, Mexico

[6] Vinmec Res Inst Stem Cell & Gene Technol, Hanoi, Vietnam

来源：

NATURE GENETICS | 2017年 / 49卷 / 07期

关键词：

CHROMOSOME CONFORMATION CAPTURE; HIGH-THROUGHPUT; R/BIOCONDUCTOR PACKAGE; CHROMATIN INTERACTIONS; GENE-EXPRESSION; SEQUENCING DATA; TRANSCRIPTION; ARCHITECTURE; DISCOVERY; RNA;

D O I：

10.1038/ng.3884

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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.

引用

页码：1073 / +

页数：12

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