"Transcription factor Ap2b regulates the mouse autosomal recessive poly" by Maoqing Wu, Naoe Harafuji et al.
 

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

Document Type

Journal Article

Publication Date

1-1-2022

Journal

Frontiers in molecular biosciences

Volume

9

DOI

10.3389/fmolb.2022.946344

Keywords

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

Abstract

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.

Department

Genomics and Precision Medicine

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