Chromatin structure regulation in transforming growth factor-β- directed epithelial-mesenchymal transition

Miroslav Blumenberg, Shujuan Gao, Kathleen Dickman, Arthur P. Grollman, Erwin P. Bottinger, Jiri Zavadil

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Epithelial-mesenchymal transitions (EMTs) occur in organogenesis throughout embryonic development and are recapitulated during epithelial tissue injury and in carcinoma progression. EMTs are regulated by complex, precisely orchestrated cell signaling and gene expression networks, with the participation of key developmental pathways. Here we review context-dependent modules of gene regulation by hairy/enhancer-of-split-related (H/E(spl)) repressors downstream of transforming growth factor-β (TGF-β)/Smad and Notch signals in EMT and in other phenotype transitions such as differentiation and cancer. Based on multiple models of disease-related EMT, we propose that Polycomb group epigenetic silencers and histone-lysine methyl-transferases EZH1 and EZH2 are candidate targets of H/E(spl)-mediated transcriptional repression, in a process accompanied by replacement of modified core histone H3 with de novo synthesized histone variant H3.3B. Finally, we discuss the potential significance of this scenario for EMT in the light of recent findings on gene regulation by histone modifications and chromatin structure changes.

Original languageEnglish
Pages (from-to)162-174
Number of pages13
JournalCells Tissues Organs
Volume185
Issue number1-3
DOIs
StatePublished - Jun 2007

Keywords

  • Aristolochic acid-I
  • Chromatin
  • Epithelial-mesenchymal transition
  • Gene expression regulation
  • Hairy/enhancer-of-split-related repressors
  • Histones
  • Polycomb-group proteins
  • Transforming growth factor-β

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