The role of ZEB transcription factors in epigenetic chromatin remodeling and gene expression regulation during EMT (G050217N)

Epithelial-to-mesenchymal transition (EMT) is a process leading to a reversible switch from a polarized epithelial phenotype to a motile and mesenchymal phenotype. EMT is an essential process in embryonic development and in adult life in several physiological (e.g. wound healing) and pathological processes (e.g. fibrosis, cancer progression). In our research group we are focusing on the Zinc finger E-box binding homeobox (ZEB) family represented by ZEB1 and ZEB2. We previously have shown that ZEB factors regulate specific cellular aspects of EMT and can have opposite effects in a tissue-specific manner. However, ZEBs functional specificity is so far not well understood. Structurally, ZEBs are composed of two highly homologous zinc-finger domains that can bind DNA with high affinity leading to gene repression. Other protein domains seem more specific for the different ZEB factors to interact with particular epigenetic regulators or other TFs. Epigenetics refers to heritable changes in gene activity and expression that occur without affecting the DNA sequence (e.g. Histone modification, DNA methylation). We believe that ZEBs function and specificity during EMT resides in a specific interaction with such epigenetic regulators. In this project we want to unravel the particular role of ZEB1 and ZEB2 on gene regulation during the EMT process with a genome wide sequencing approach and emphasize on the importance of epigenetic regulators and TF binding partners for ZEB function.