ZNF827-dependent splicing dynamics are critical for EMT during development and disease [RNA-seq]

Epithelial to mesenchymal transition (EMT) is a multi-step process during which epithelial cells become mesenchymal stem cells. EMT is involved during embryonic development, wound healing, fibrosis and tumor metastasis. Here we show that ZNF827, a C2H2-zinc finger containing protein, is critical for molecular and phenotypic changes underlying EMT. We demonstrate that ZNF827 depletion suppresses tumor metastasis and cortical neurogenesis in vivo by impairing EMT. Further analysis showed that ZNF827 is critical for global alternative splicing (AS) during EMT. We further reveal that ZNF827 interacts with various components of core splicing machinery and directly binds DNA. ZNF827 depletion leads to alteration of epigenetic landscape at its target genomic region which might be important for alternative splicing of these target genes. Our findings established ZNF827 as a novel regulator of AS during development and disease contexts of EMT. 3 replicates each for HMLE cells Untreated, d4 TGF-B treated and transfected with siControl or siZNF827