title: Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor.
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.
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruf
authors.forename: Orsolya
authors.initials: O
authors.lastname: Symmons
authors.forename: Veli Vural
authors.initials: VV
authors.lastname: Uslu
authors.forename: Dirk
authors.initials: D
authors.lastname: Dolle
authors.forename: Chloé
authors.initials: C
authors.lastname: Hot
authors.forename: Laurence
authors.initials: L
authors.lastname: Ettwiller
authors.forename: François
authors.initials: F
authors.lastname: Spitz
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004251:DNA Transposable Elements / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005821:Genetic Techniques; D016678:Genome; D005865:Gestational Age; D006801:Humans; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D012045:Regulatory Sequences, Nucleic Acid; D019895:Transposases / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D019895:Transposases; C494471:sleeping beauty transposase, human