However, little is known about the regulation of YAP1 on the transcriptional level. The activity of YAP1 is affected by protein–protein interactions, phosphorylation, and re-localization of YAP1. YAP1 is expressed in all human tissues, with a relatively medium expression in the intestinal tissue. YAP1 is a co-transcription factor that interacts with the TEA domain transcription factor (TEAD) family members to regulate the expression of many genes, especially those important for proliferation, adhesion, migration and the extracellular matrix organization.
Extra- and intracellular growth signals are relayed through the Hippo phosphorylation kinase cascade that inactivates the two downstream effectors Yes-associated protein 1 (YAP1) and WW domain containing transcription regulator 1 (WWTR1). It acts as a switch between proliferation and differentiation. The Hippo pathway is a signaling pathway that is important for tissue homeostasis, regulation of organ size and tumorigenesis. Additionally, CDX2 and HNF4α binding are important for the YAP1 enhancer activity in intestinal epithelial 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. It was found by chromatin immunoprecipitation experiments that CDX2 and HNF4α bind to the YAP1 enhancer in Caco-2 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.
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. 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. The aim of this study to identify gene control regions in the YAP1 gene and transcription factors important for intestinal expression. Nevertheless, little is known about the transcriptional regulation of YAP1 in intestinal cells. 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. The Hippo pathway is important for tissue homeostasis, regulation of organ size and growth in most tissues.
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