Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor |
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Authors: | Ruf Sandra Symmons Orsolya Uslu Veli Vural Dolle Dirk Hot Chloé Ettwiller Laurence Spitz François |
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Institution: | Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. |
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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. |
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