Next Article in Journal
Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases
Next Article in Special Issue
Ubiquitination and Long Non-coding RNAs Regulate Actin Cytoskeleton Regulators in Cancer Progression
Previous Article in Journal
Potential Mechanisms of T Cell-Mediated and Eosinophil-Independent Bronchial Hyperresponsiveness
Previous Article in Special Issue
New Insights into the Role of Polybromo-1 in Prostate Cancer
Article Menu
Issue 12 (June-2) cover image

Export Article

Open AccessArticle

HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity

Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark
Department of Clinical Immunology, Næstved Hospital, Ringstedgade 77B, 4700 Næstved, Denmark
Department of Surgery, Center for Surgical Science, Enhanced Perioperative Oncology (EPEONC) Consortium, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(12), 2981;
Received: 6 May 2019 / Revised: 10 June 2019 / Accepted: 16 June 2019 / Published: 18 June 2019
PDF [2608 KB, uploaded 20 June 2019]


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. View Full-Text
Keywords: Hippo pathway; intestinal epithelium; yes-associated protein 1 (YAP1); transcriptional regulation; gene regulation; transcription factor; cellular regulation Hippo pathway; intestinal epithelium; yes-associated protein 1 (YAP1); transcriptional regulation; gene regulation; transcription factor; cellular regulation

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Larsen, S.; Davidsen, J.; Dahlgaard, K.; Pedersen, O.B.; Troelsen, J.T. HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity. Int. J. Mol. Sci. 2019, 20, 2981.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top