title: Comparative genomic analysis of vertebrate Hox3 and Hox4 genes.
abstract: We used a comparative genomic approach to identify putative cis-acting regulatory sequences of the zebrafish hoxb3a and hoxb4a genes. We aligned genomic sequences spanning the clustered Hoxb1 to Hoxb5 genes from pufferfish, mice, and humans with the zebrafish hoxba and hoxbb cluster sequences. We identified multiple blocks of conserved sequences in non-coding regions within and surrounding the Hoxb3/b4 gene locus; a subset of these blocks are conserved in the zebrafish hoxbb cluster, despite loss of hoxb3/b4 genes. Overall, we find that the architecture of the Hoxb3/b4 loci and of the conserved sequence elements is very similar in teleosts and mammals. Our analyses also revealed two alternative transcripts of the zebrafish hoxb3a gene and an exon sequence unusually located 10 kb upstream of adjacent hoxb4a; an equivalent murine Hoxb3 exon has not yet been confirmed. We show that many of the Hoxb3/b4 conserved non-coding sequences correlate with functional neural enhancers previously described in the mouse. Further, within the conserved non-coding sequences we have identified binding sites for transcription factors, including Kreisler/Valentino, Krox20, Hox, and Pbx, some of which had not been previously described for the mouse. Finally, we demonstrate that the regulatory sequences of zebrafish hoxa3a are divergent with respect to the mouse ortholog Hoxa3, or the paralog hoxb3a. Despite limited conservation of regulatory sequences, zebrafish hoxa3a and hoxb3a genes share very similar expression profiles.
authors.affiliation: Department of Physiology and Neuroscience, NYU Medical School, New York, New York 10016, USA.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hadrys
authors.forename: Victoria
authors.initials: V
authors.lastname: Prince
authors.forename: Michael
authors.initials: M
authors.lastname: Hunter
authors.forename: Robert
authors.initials: R
authors.lastname: Baker
authors.forename: Silke
authors.initials: S
authors.lastname: Rinkwitz
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D040461:Gene Components; D020869:Gene Expression Profiling; D015723:Gene Library; D005801:Genes, Homeobox / Q000235:genetics*; D016678:Genome; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D023721:Tetraodontiformes / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004247:DNA