HNF-1beta Regulates Transcription of the PKD Modifier Gene Kif12

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2008 Nov 14

PMID 19005009

Citations 34

Authors

Yimei Gong

Zhendong Ma

Vishal Patel

Evelyne Fischer

Thomas Hiesberger

Marco Pontoglio

Peter Igarashi

Affiliations

Soon will be listed here.

Abstract

Hepatocyte nuclear factor-1beta (HNF-1beta) is a transcription factor that regulates gene expression in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1beta lead to a syndrome of inherited renal cysts and diabetes and are also a common cause of sporadic renal dysplasia. The full complement of target genes responsible for the functions of HNF-1beta, however, is incompletely defined. Using a functional genomics approach involving chromatin immunoprecipitation and promoter arrays, combined with gene expression profiling, we found that an HNF-1beta target gene in the kidney is kinesin family member 12 (Kif12), a gene previously identified as a candidate modifier gene in the cpk mouse model of polycystic kidney disease. Mutations of HNF-1beta inhibited Kif12 transcription in both cultured cells and knockout mice by altering co-factor recruitment and histone modification. Because kinesin-12 family members participate in orienting cell division, downregulation of Kif12 may underlie the abnormal planar cell polarity observed in cystic kidney diseases.

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