The Histone Variant H2A.Z Is a Master Regulator of the Epithelial-Mesenchymal Transition

Renae Domaschenz, Sebastian Kurscheid, Maxim Nekrasov, Shuyi Han, David J. Tremethick*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    41 Citations (Scopus)

    Abstract

    Epithelial-mesenchymal transition (EMT) is a profound example of cell plasticity that is crucial for embryonic development and cancer. Although it has long been suspected that chromatin-based mechanisms play a role in this process, no master regulator that can specifically regulate EMT has been identified to date. Here, we show that H2A.Z can coordinate EMT by serving as either an activator or repressor of epithelial or mesenchymal gene expression, respectively. Following induction of EMT by TGF-β, we observed an unexpected loss of H2A.Z across both downregulated epithelial and upregulated mesenchymal promoters. Strikingly, the repression of epithelial gene expression was associated with reduction of H2A.Z upstream of the transcription start site (TSS), while the activation of mesenchymal gene expression was dependent on removal of H2A.Z downstream of the TSS. Therefore, the ability of H2A.Z to regulate EMT is dependent on its position, either upstream or downstream of the TSS. EMT is one of the most intensely studied differentiation-dedifferentiation processes. Domaschenz et al. now demonstrate that H2A.Z has the unique ability to simultaneously serve as either an activator or a repressor of epithelial or mesenchymal gene expression, respectively.

    Original languageEnglish
    Pages (from-to)943-952
    Number of pages10
    JournalCell Reports
    Volume21
    Issue number4
    DOIs
    Publication statusPublished - 24 Oct 2017

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