Histone Marks Regulate the Epithelial-to-Mesenchymal Transition via Alternative Splicing

Histone modifications have long been shown to impact final splicing decisions via modulation of RNA polymerase II elongation rate and/or recruitment the regulators their binding sites. However there is little evidence driving role these chromatin in inducing changes necessary for a switch cell’s phenotype. Taking advantage epithelial-to-mesenchymal transition (EMT), reversible cell reprogramming intimately involved early development and cancer metastasis, we found that dynamic specific histone marks, namely H3K27ac H3K27me3, were responsible key EMT. Using CRISPR epigenome editing tools, showed single change H3K27ac/me3 levels just at alternatively spliced exon was sufficient induce capable recapitulating important aspects EMT, such as motility invasiveness. This mark-dependent effect highly mediated by direct regulator PTB its Taken together, results support novel H3K27 marks phenotype regulation alternative splicing. We propose nature epigenetic rapid, reversible, mechanism coordinate response cell-extrinsic cues, induction