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

Oliver G. McDonald, Hao Wu, Winston Timp, Akiko Doi, Andrew P. Feinberg

Research output: Contribution to journalArticlepeer-review

274 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)867-874
Number of pages8
JournalNature Structural and Molecular Biology
Issue number8
StatePublished - Aug 2011
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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