Conservation of RET regulatory function from human to zebrafish without sequence similarity.
Evolutionary sequence conservation is an accepted criterion to identify noncoding regulatory sequences. We have used a transposon-based transgenic assay in zebrafish to evaluate noncoding sequences at the zebrafish ret locus, conserved among teleosts, and at the human RET locus, conserved among mammals. Most teleost sequences directed ret-specific reporter gene expression, with many displaying overlapping regulatory control. The majority of human RET noncoding sequences also directed ret-specific expression in zebrafish. Thus, vast amounts of functional sequence information may exist that would not be detected by sequence similarity approaches.
Fisher
Shannon
S
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. sfisher@jhmi.edu
Grice
Elizabeth A
EA
Vinton
Ryan M
RM
Bessling
Seneca L
SL
McCallion
Andrew S
AS
D000818:Animals; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D023741:Takifugu / Q000235:genetics; D019076:Transgenes; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human