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This article is part of the supplement: Transposons in vertebrate functional genomics

Review

Retroviral enhancer detection insertions in zebrafish combined with comparative genomics reveal genomic regulatory blocks - a fundamental feature of vertebrate genomes

Hiroshi Kikuta12, David Fredman13, Silke Rinkwitz1, Boris Lenhard13* and Thomas S Becker1*

Author Affiliations

1 Sars Centre for Marine Molecular Biology, University of Bergen, Thormoehlensgate, 5008 Bergen, Norway

2 Division of Molecular and Developmental Biology, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan

3 Computational Biology Unit, University of Bergen, Thormoehlensgate, 5008 Bergen, Norway

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Genome Biology 2007, 8(Suppl 1):S4  doi:10.1186/gb-2007-8-s1-s4

Published: 31 October 2007

Abstract

A large-scale enhancer detection screen was performed in the zebrafish using a retroviral vector carrying a basal promoter and a fluorescent protein reporter cassette. Analysis of insertional hotspots uncovered areas around developmental regulatory genes in which an insertion results in the same global expression pattern, irrespective of exact position. These areas coincide with vertebrate chromosomal segments containing identical gene order; a phenomenon known as conserved synteny and thought to be a vestige of evolution. Genomic comparative studies have found large numbers of highly conserved noncoding elements (HCNEs) spanning these and other loci. HCNEs are thought to act as transcriptional enhancers based on the finding that many of those that have been tested direct tissue specific expression in transient or transgenic assays. Although gene order in hox and other gene clusters has long been known to be conserved because of shared regulatory sequences or overlapping transcriptional units, the chromosomal areas found through insertional hotspots contain only one or a few developmental regulatory genes as well as phylogenetically unrelated genes. We have termed these regions genomic regulatory blocks (GRBs), and show that they underlie the phenomenon of conserved synteny through all sequenced vertebrate genomes. After teleost whole genome duplication, a subset of GRBs were retained in two copies, underwent degenerative changes compared with tetrapod loci that exist as single copy, and that therefore can be viewed as representing the ancestral form. We discuss these findings in light of evolution of vertebrate chromosomal architecture and the identification of human disease mutations.