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• W2068087430 abstract "Alterations in DNA and histone modifications are known to occur during development and in disease. The changes that occur during TGF-β–triggered epithelial-to-mesenchymal transition are now examined on a global scale. DNA methylation remained relatively stable, but major changes in histone modifications, dependent on the histone demethylase Lsd1, were observed, particularly in large, organized heterochromatic Lys9-methylated regions. 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." @default.
• W2068087430 created "2016-06-24" @default.
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• W2068087430 date "2011-07-03" @default.
• W2068087430 modified "2023-10-17" @default.
• W2068087430 title "Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition" @default.
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• W2068087430 doi "https://doi.org/10.1038/nsmb.2084" @default.
• W2068087430 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3150339" @default.
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