title: Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.
abstract: Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.
authors.affiliation: Department of Medicine, Addenbrookes Hospital, Cambridge, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Aparicio
authors.forename: A
authors.initials: A
authors.lastname: Morrison
authors.forename: A
authors.initials: A
authors.lastname: Gould
authors.forename: J
authors.initials: J
authors.lastname: Gilthorpe
authors.forename: C
authors.initials: C
authors.lastname: Chaudhuri
authors.forename: P
authors.initials: P
authors.lastname: Rigby
authors.forename: R
authors.initials: R
authors.lastname: Krumlauf
authors.forename: S
authors.initials: S
authors.lastname: Brenner
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005400:Fishes, Poisonous / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D012333:RNA, Messenger