title: Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition.
abstract: Epithelial-to-mesenchymal transition (EMT) is an extreme example of cell plasticity that is important for normal development, injury repair and malignant progression. Widespread epigenetic reprogramming occurs during stem cell differentiation and malignant transformation, but EMT-related epigenetic reprogramming is poorly understood. Here we investigated epigenetic modifications during EMT mediated by transforming growth factor beta. Although DNA methylation was unchanged during EMT, we found a global reduction in the heterochromatin mark H3 Lys9 dimethylation (H3K9Me2), an increase in the euchromatin mark H3 Lys4 trimethylation (H3K4Me3) and an increase in the transcriptional mark H3 Lys36 trimethylation (H3K36Me3). These changes depended largely on lysine-specific demethylase-1 (Lsd1), and loss of Lsd1 function had marked effects on EMT-driven cell migration and chemoresistance. Genome-scale mapping showed that chromatin changes were mainly specific to large organized heterochromatin K9 modifications (LOCKs), which suggests that EMT is characterized by reprogramming of specific chromatin domains across the genome.
authors: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Oliver G
authors: OG
authors: McDonald
authors: Hao
authors: H
authors: Wu
authors: Winston
authors: W
authors: Timp
authors: Akiko
authors: A
authors: Doi
authors: Andrew P
authors: AP
authors: Feinberg
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D006657:Histones; D016212:Transforming Growth Factor beta; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating