Investigating CDX2 association sites to identify regulatory elements of YAP1 in Caco-2 and LS174T colon cancer cell lines}

Andreas Kaas-Mason, Sofia Ramirez-Ekner, Stephanie Berntsen Croft & Anna Svetlova

Studenteropgave: Fagmodulprojekt

Abstrakt

Yes-associated protein 1 (YAP1) is a downstream effector molecule of the Hippo signaling pathway. YAP1 has been linked to several forms of cancer such as colorectal cancer (CRC), as it plays a major role in cell proliferation and regeneration in the colon. The transcription factor Caudal type homeobox 2 (CDX2) is an intestinal specific transcription factor that is important for the regulation of genes responsible for intestinal cell differentiation and proliferation. CDX2 has been shown to regulates YAP1 but the mechanism of how it regulate YAP1 is still unknown. Chromatin Immunoprecipitation-Sequencing (ChIP-Seq) data showed potential regulatory elements of where CDX2 associates with YAP1. Two sequences located in introns 1 and 3 were chosen for a promoter reporter assay to investigate the presence of a regulatory element and to determine the function of it. Results from a Dual-Light assay suggests that the sequence located within intron 3 on YAP1 has potential repressive activity in LS174T cells, but has no specific function reported in Caco-2 cells. These results suggest that individual regulatory elements can be cell line specific. Further investigations need to be made in order to come to a more clear conclusion on how exactly CDX2 associates with the specific sequences of YAP1. Understanding the transcriptional factor network in the intestine and YAP1 regulation by CDX2 could help to develop YAP1 targeted CRC treatment.

UddannelserMolekylærbiologi, (Bachelor/kandidatuddannelse) Bachelor
SprogEngelsk
Udgivelsesdato27 maj 2019
Antal sider30
VejledereSylvester Larsen