CCAAT enhansir bağlayici protein alfa (CEBPA)'nin transkripsiyonel regülasyonu

Comparative genomics is a well-known method with diverse applications. By comparing intergenic DNA sequences among different species, one can identify potential regulatory sequences such as enhancers, by assuming that conserved function would lead to conserved expression, thus conserved regulation. EMT and MET are crucial biological processes where the cells can alter their expressed genes and consequently shift between epithelial and mesenchymal phenotypes. Since the E-cadherin expression -which is the identifier marker for epithelial cells- sits on the center of the questions that need to be answered, any factors that were known to play a role affecting the E-cad expression needs to be addressed in order to reveal the mechanisms of MET process. Cebpa was shown to be correlated with E-cadherin in MET in our previous project, where Cebpa has a high correlation with epithelial phenotype, and increased expression alongside with Cdh1 (E-cad) in MET, and decreased levels in EMT. In the view of such evidence, it was hypothesized that Cebpa might have an essential role in EMT-MET processes and its regulation and function can be crucial in MET. The in-vitro experiments of Cebpa knockdown in MET also showed supporting results for the hypothesis. When Cebpa was silenced in mesenchymal state cells, they were not able to return to their epithelial state in MET, the process was blocked. Therefore the regulation of Cebpa was needed to be addressed more. In order to identify putative regulators of Cebpa, cis-acting elements and trans-acting factors were identified among conserved regions of Cebpa 23kb region and common TFBSs were observed. GEO datasets of publicly available gene expression profiles of the same tissue where Cebpa was known to be expressed in high levels were analyzed with bioinformatics tools and common TFs were identified among the datasets. The results of conserved regions and GEO datasets were compared and putative regulator(s) of Cebpa was selected. According to the findings of this study, Jarid2 is a possible candidate of Cebpa regulation since it was one of the conserved TFs both in location and in sequence information. The two factors are both have a role in differentiation, transcriptional repression and early development, and mutation in Prc2 which is highly interacting with Jarid2 also causes mutation in Cebpa that leads a way to Acute Myeloid Leukemia (AML).