Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition

Nat Struct Mol Biol. 2011 Jul 3;18(8):867-74. doi: 10.1038/nsmb.2084.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement / genetics
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial-Mesenchymal Transition*
  • Histone Demethylases
  • Histones / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects
  • Oxidoreductases, N-Demethylating / genetics
  • Oxidoreductases, N-Demethylating / physiology
  • Transforming Growth Factor beta / pharmacology


  • Histones
  • Transforming Growth Factor beta
  • Histone Demethylases
  • KDM1a protein, mouse
  • Oxidoreductases, N-Demethylating

Associated data

  • GEO/GSE27968
  • GEO/GSE28581