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HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 12, Larsen, S, Davidsen, J, Dahlgaard, K, Pedersen, O B & Troelsen, J T 2019, ' HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity ', International Journal of Molecular Sciences, vol. 20, no. 12, 2981 . https://doi.org/10.3390/ijms20122981, International Journal of Molecular Sciences, Vol 20, Iss 12, p 2981 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- The Hippo pathway is important for tissue homeostasis, regulation of organ size andgrowth in most tissues. The co‐transcription factor yes‐associated protein 1 (YAP1) serves as a maindownstream effector of the Hippo pathway and its dysregulation increases cancer development andblocks colonic tissue repair. Nevertheless, little is known about the transcriptional regulation ofYAP1 in intestinal cells. The aim of this study to identify gene control regions in the YAP1 gene andtranscription factors important for intestinal expression. Bioinformatic analysis of caudal typehomeobox 2 (CDX2) and hepatocyte nuclear factor 4 alpha (HNF4&alpha<br />) chromatin immunoprecipitatedDNA from differentiated Caco‐2 cells revealed potential intragenic enhancers in the YAP1 gene.Transfection of luciferase‐expressing YAP1 promoter‐reporter constructs containing the potentialenhancer regions validated one potent enhancer of the YAP1 promoter activity in Caco‐2 and T84cells. Two potential CDX2 and one HNF4&alpha<br />binding sites were identified in the enhancer by in silicotranscription factor binding site analysis and protein‐DNA binding was confirmed in vitro usingelectrophoretic mobility shift assay. It was found by chromatin immunoprecipitation experimentsthat CDX2 and HNF4&alpha<br />bind to the YAP1 enhancer in Caco‐2 cells. These results reveal a previouslyunknown enhancer of the YAP1 promoter activity in the YAP1 gene, with importance for highexpression levels in intestinal epithelial cells. Additionally, CDX2 and HNF4&alpha<br />binding areimportant for the YAP1 enhancer activity in intestinal epithelial cells.
- Subjects :
- Hippo pathway
Catalysis
Inorganic Chemistry
lcsh:Chemistry
Cellular regulation
Transcriptional regulation
intestinal epithelium
transcriptional regulation
Intestinal epithelium
Physical and Theoretical Chemistry
Enhancer
CDX2
Molecular Biology
Transcription factor
lcsh:QH301-705.5
Spectroscopy
transcription factor
Regulation of gene expression
Hippo signaling pathway
cellular regulation
Chemistry
yes-associated protein 1 (YAP1)
yes‐associated protein 1 (YAP1)
Organic Chemistry
General Medicine
Computer Science Applications
Chromatin
Cell biology
Gene regulation
DNA binding site
lcsh:Biology (General)
lcsh:QD1-999
Yes‐associated protein 1 (YAP1)
gene regulation
Chromatin immunoprecipitation
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....6571b87e911255c5919ab0bb220a85db
- Full Text :
- https://doi.org/10.3390/ijms20122981