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

Document Type

Journal Article

Publication Date



Frontiers in molecular biosciences






Cys1; Pkhd1; TFAP2B; Tfap2b; autosomal recessive polycystic kidney disease (ARPKD)


Transcription factor Ap2b (TFAP2B), an AP-2 family transcription factor, binds to the palindromic consensus DNA sequence, 5'-GCCNGGC-3'. 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' Rapid Amplification of cDNA Ends (5'RACE); 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.


Genomics and Precision Medicine