MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition

Huacheng Luo, Anitha K. Shenoy, Xuehui Li, Yue Jin, Lihua Jin, Qingsong Cai, Ming Tang, Yang Liu, Hao Chen, David Reisman, Lizi Wu, Edward Seto, Yi Qiu, Yali Dou, Robert A Casero, Jianrong Lu

Research output: Contribution to journalArticle

Abstract

The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby suppressing EMT and tumor invasion. Conversely, MOF depletion enhances EMT and tumor metastasis. In human cancer, high MOF expression correlates with epithelial markers and a favorable prognosis. These findings provide insight into the regulation of LSD1 and EMT and identify MOF as a critical suppressor of EMT and tumor progression.

Original languageEnglish (US)
Pages (from-to)2665-2678
Number of pages14
JournalCell Reports
Volume15
Issue number12
DOIs
StatePublished - Jun 21 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Luo, H., Shenoy, A. K., Li, X., Jin, Y., Jin, L., Cai, Q., Tang, M., Liu, Y., Chen, H., Reisman, D., Wu, L., Seto, E., Qiu, Y., Dou, Y., Casero, R. A., & Lu, J. (2016). MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition. Cell Reports, 15(12), 2665-2678. https://doi.org/10.1016/j.celrep.2016.05.050