56 research outputs found

    Transcription factor Ap2b regulates the mouse autosomal recessive polycystic kidney disease genes, Pkhd1 and Cys1

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    Transcription factor Ap2b (TFAP2B), an AP-2 family transcription factor, binds to the palindromic consensus DNA sequence, 5\u27-GCCNGGC-3\u27. Mice lacking functional gene die in the perinatal or neonatal period with cystic dilatation of the kidney distal tubules and collecting ducts, a phenotype resembling autosomal recessive polycystic kidney disease (ARPKD). Human ARPKD is caused by mutations in , , and which are conserved in mammals. In this study, we examined the potential role of TFAP2B as a common regulator of and We determined the transcription start site (TSS) of using 5\u27 Rapid Amplification of cDNA Ends (5\u27RACE); the TSS of has been previously established. Bioinformatic approaches identified -regulatory elements, including two TFAP2B consensus binding sites, in the upstream regulatory regions of both and . Based on reporter gene assays performed in mouse renal collecting duct cells (mIMCD-3), TFAP2B activated the and promoters and electromobility shift assay (EMSA) confirmed TFAP2B binding to the identified sites. These results suggest that participates in a renal epithelial cell gene regulatory network that includes and . Disruption of this network impairs renal tubular differentiation, causing ductal dilatation that is the hallmark of recessive PKD

    The draft genome of Ciona intestinalis: Insights into chordate and vertebrate origins

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    The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains similar to16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi
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