title: Chromatin structure regulation in transforming growth factor-beta-directed epithelial-mesenchymal transition.
abstract: Epithelial-mesenchymal transitions (EMTs) occur in organogenesis throughout embryonic development and are recapitulated during epithelial tissue injury and in carcinoma progression. EMTs are regulated by complex, precisely orchestrated cell signaling and gene expression networks, with the participation of key developmental pathways. Here we review context-dependent modules of gene regulation by hairy/enhancer-of-split-related (H/E(spl)) repressors downstream of transforming growth factor-beta (TGF-beta)/Smad and Notch signals in EMT and in other phenotype transitions such as differentiation and cancer. Based on multiple models of disease-related EMT, we propose that Polycomb group epigenetic silencers and histone-lysine methyl-transferases EZH1 and EZH2 are candidate targets of H/E(spl)-mediated transcriptional repression, in a process accompanied by replacement of modified core histone H3 with de novo synthesized histone variant H3.3B. Finally, we discuss the potential significance of this scenario for EMT in the light of recent findings on gene regulation by histone modifications and chromatin structure changes.
authors.affiliation: Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Blumenberg
authors.forename: Shujuan
authors.initials: S
authors.lastname: Gao
authors.forename: Kathleen
authors.initials: K
authors.lastname: Dickman
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Grollman
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Bottinger
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007672:Kidney Cortex / Q000166:cytology; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D016212:Transforming Growth Factor beta