HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

The Hippo pathway is important for tissue homeostasis, regulation of organ size and growth in most tissues. The co‐transcription factor yes‐associated protein 1 (YAP1) serves as a main downstream effector of the Hippo pathway and its dysregulation increases cancer development and blocks colonic tissue repair. Nevertheless, little is known about the transcriptional regulation of YAP1 in intestinal cells. The aim of this study to identify gene control regions in the YAP1 gene and transcription factors important for intestinal expression. Bioinformatic analysis of caudal type homeobox 2 (CDX2) and hepatocyte nuclear factor 4 alpha (HNF4α) chromatin immunoprecipitated DNA from differentiated Caco‐2 cells revealed potential intragenic enhancers in the YAP1 gene. Transfection of luciferase‐expressing YAP1 promoter‐reporter constructs containing the potential enhancer regions validated one potent enhancer of the YAP1 promoter activity in Caco‐2 and T84 cells. Two potential CDX2 and one HNF4α binding sites were identified in the enhancer by in silico transcription factor binding site analysis and protein‐DNA binding was confirmed in vitro using electrophoretic mobility shift assay. It was found by chromatin immunoprecipitation experiments that CDX2 and HNF4α bind to the YAP1 enhancer in Caco‐2 cells. These results reveal a previously unknown enhancer of the YAP1 promoter activity in the YAP1 gene, with importance for high expression levels in intestinal epithelial cells. Additionally, CDX2 and HNF4α binding are important for the YAP1 enhancer activity in intestinal epithelial cells.

Original languageEnglish
Article number2981
JournalInternational Journal of Molecular Sciences
Volume20
Issue number12
Number of pages17
ISSN1661-6596
DOIs
Publication statusPublished - 2019

    Research areas

  • Cellular regulation, Gene regulation, Hippo pathway, Intestinal epithelium, Transcription factor, Transcriptional regulation, Yes‐associated protein 1 (YAP1)

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 240951163