Mezenkimal-epitelyal dönüşümünü (MET) kontrol eden transkripsiyonel ağların belirlenmesi

Dynamic fluctuations through cellular plasticity and intermolecular changes within the gene regulatory networks are utilized by conserved and complex mechanisms in which cells switch between different phenotypes without altering the genotype. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) cellular programs, in which E- cadherin (E-cad) is the hallmark, endow with phenotypic plasticity. While much attention is being paid to EMT regulation, little attention is paid to the mechanisms underlying MET regulation. This thesis explores the dynamic MET process from a distinct viewpoint from its counterparts in the literature. It is based on identifying a basic transcriptional network that controls cells' epithelial stability, which might play a crucial role in initiating the MET process. We carried out a comprehensive approach consisting of data mining, in silico analyses, and in- vitro experimental studies to determine the possible network members and verify their relationships. Analysis of gene expression profiles from NMuMG cells and the other datasets obtained from the literature, followed by loss of function experiments, revealed that transcription factors such as Elf3, Grhl3, Ovol2, Ahr, and Nfya are regulators of the MET process. Some transcriptional nodes were identified where Grhl3 and Elf3 are in the center of the network. It is also revealed that Grhl3 and Ovol2 transcriptional factors are most likely to collaborate in development processes and transcriptional regulation of important biological processes such as EMT. In conclusion, our findings present novel insights into the regulation of MET and reveal some transcription factors such as Elf3 as an indispensable guardian of the epithelial state within a transcriptional network. Keywords: MET, Transcriptional Networks, EMT, Elf3, Grhl3, Ovol2