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PMID: 21423180 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 43 ·No. 4 ·2011-03-20 ·Pages 379-86

Ruf S, Symmons O, Uslu VV, Dolle D, Hot C, Ettwiller L, Spitz F

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.

MeSH Terms
Animals Chromosome Mapping DNA Transposable Elements/genetics Enhancer Elements, Genetic Female Gene Expression Regulation, Developmental Genes, Reporter Genetic Techniques Genome Gestational Age Humans Lac Operon Mice Mice, Transgenic Pregnancy Regulatory Sequences, Nucleic Acid Transposases/genetics
Chemicals
DNA Transposable Elements Transposases sleeping beauty transposase, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ruf Sandra
Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Symmons Orsolya
Uslu Veli Vural
Dolle Dirk
Hot Chloé
Ettwiller Laurence
Spitz François
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.790
Published
2011-03-20
Epub
2011-00-20
Pages
379-86
Language
English
Region
United States
NLM ID
9216904
Subset
IM
External Links
PubMed source DOI: 10.1038/ng.790 View journal details
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