Epigenetic regulation of epithelial-mesenchymal transition: Focusing on hypoxia and TGF-β signaling

Yueh Te Lin, Kou Juey Wu*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

111 Scopus citations

Abstract

Epithelial-mesenchymal transition (EMT) is an important process triggered during cancer metastasis. Regulation of EMT is mostly initiated by outside signalling, including TGF-β, growth factors, Notch ligand, Wnt, and hypoxia. Many signalling pathways have been delineated to explain the molecular mechanisms of EMT. In this review, we will focus on the epigenetic regulation of two critical EMT signalling pathways: Hypoxia and TGF-β. For hypoxia, hypoxia-induced EMT is mediated by the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5 coupled with the presence of histone 3 lysine 4 acetylation (H3K4Ac) mark that labels the promoter regions of various traditional EMT marker genes (e.g. CDH1, VIM). Recently identified new hypoxia-induced EMT markers belong to transcription factors (e.g. SMO, GLI1) that mediate EMT themselves. For TGF-β-induced, global chromatin changes, removal of a histone variant (H2A.Z), and new chromatin modifiers (e.g. UTX, Rad21, PRMT5, RbBP5, etc) are identified to be crucial for the regulation of both EMT transcription factors (EMT-TFs) and EMT markers (EMT-Ms). The epigenetic mechanisms utilized in these two pathways may serve as good model systems for other signalling pathways and also provide new potential therapeutic targets.

Original languageEnglish
Article number39
JournalJournal of Biomedical Science
Volume27
Issue number1
DOIs
StatePublished - 02 03 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s).

Keywords

  • ChIP
  • Epigenetic regulation
  • Epithelial-mesenchymal transition
  • H2A.Z
  • H3K4Ac
  • HDAC3
  • HIF-1α
  • Hypoxia
  • LSD1
  • TGF-β
  • WDR5

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