Characterizing the role gene networks that maintain the epithelial phenotype have in facilitating the molecular EMT program
Research Project by Nicole Vincent-Jordan
Epithelial-mesenchymal transition (EMT) is a fundamental developmental program that converts epithelial cells to motile mesenchymal cells for the formation of developing organs during embryogenesis and for the conversion of carcinoma cells during invasion and metastasis. Relevant to EMT, we previously characterized the developmental dysregulation of a genetically engineered MAP3K4-inactive (KI4) mouse, which exhibits neural tube and mesoderm closure defects, as well as craniofacial (neural crest) and placental implantation (trophoblast) abnormalities. Trophoblast stem cells isolated from the placentas of KI4 mice (TSKI4 cells) exhibit the traditional hallmarks of EMT, including loss of the epithelial marker E-cadherin, increased cellular invasiveness and increased expression of the mesenchymal markers N-cadherin and vimentin. Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) and gene array identified the coordinated loss of H2B lysine 5 acetylation (H2BK5Ac) with the repression of a network of genes responsible for maintenance of the epithelial phenotype. This gene network is also present in the newly identified claudin-low breast cancer subtype, which is enriched for mesenchymal and stem cell characteristics. Therefore, the goal of current research is to functionally characterize the role of this gene network in facilitating the molecular EMT program.