Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor

• Verfasst von: Ruf, Sandra [VerfasserIn]
• Verfasst von: Dolle, Dirk-Dominik [VerfasserIn]
• Verfasst von: Ettwiller, Laurence [VerfasserIn]
• Titel: Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor
• Verf.angabe: Sandra Ruf, Orsolya Symmons, Veli Vural Uslu, Dirk Dolle, Chloé Hot, Laurence Ettwiller, François Spitz
• Umfang: 8 S.
• Fussnoten: Gesehen am 17.05.2017
• Titel Quelle: Enthalten in: Nature genetics
• Jahr Quelle: 2011
• Band/Heft Quelle: 43(2011), 4, S. 379-386
• ISSN Quelle: 1546-1718
• DOI: doi:10.1038/ng.790
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1558728481

Abstract

We present here a Sleeping Beauty-based transposition system that offers a simple and efficient way to investigate the regulatory architecture of mammalian chromosomes in vivo. With this system, we generated several hundred mice and embryos, each with a regulatory sensor inserted at a random genomic position. This large sampling of the genome revealed the widespread presence of long-range regulatory activities along chromosomes, forming overlapping blocks with distinct tissue-specific expression potentials. The presence of tissue-restricted regulatory activities around genes with widespread expression patterns challenges the gene-centric view of genome regulation and suggests that most genes are modulated in a tissue-specific manner. The local hopping property of Sleeping Beauty provides a dynamic approach to map these regulatory domains at high resolution and, combined with Cre-mediated recombination, allows for the determination of their functions by engineering mice with specific chromosomal rearrangements.