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

22 Citations (Scopus)

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

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Histone Demethylases
Epithelial-Mesenchymal Transition
Tumors
Acetylation
Histones
Genes
Neoplasms
Acetyltransferases
Methylation
Nucleosomes
Transcription
Association reactions
Down-Regulation
Epithelial Cells
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Luo, Huacheng ; Shenoy, Anitha K. ; Li, Xuehui ; Jin, Yue ; Jin, Lihua ; Cai, Qingsong ; Tang, Ming ; Liu, Yang ; Chen, Hao ; Reisman, David ; Wu, Lizi ; Seto, Edward ; Qiu, Yi ; Dou, Yali ; Casero, Robert A. ; Lu, Jianrong. / MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition. In: Cell Reports. 2016 ; Vol. 15, No. 12. pp. 2665-2678.
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author = "Huacheng Luo and Shenoy, {Anitha K.} and Xuehui Li and Yue Jin and Lihua Jin and Qingsong Cai and Ming Tang and Yang Liu and Hao Chen and David Reisman and Lizi Wu and Edward Seto and Yi Qiu and Yali Dou and Casero, {Robert A.} and Jianrong Lu",
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Luo, H, Shenoy, AK, 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, RA & Lu, J 2016, 'MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition', Cell Reports, vol. 15, no. 12, pp. 2665-2678. https://doi.org/10.1016/j.celrep.2016.05.050

MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition. / Luo, Huacheng; Shenoy, Anitha K.; Li, Xuehui; Jin, Yue; Jin, Lihua; Cai, Qingsong; Tang, Ming; Liu, Yang; Chen, Hao; Reisman, David; Wu, Lizi; Seto, Edward; Qiu, Yi; Dou, Yali; Casero, Robert A.; Lu, Jianrong.

In: Cell Reports, Vol. 15, No. 12, 21.06.2016, p. 2665-2678.

Research output: Contribution to journalArticle

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T1 - MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition

AU - Luo, Huacheng

AU - Shenoy, Anitha K.

AU - Li, Xuehui

AU - Jin, Yue

AU - Jin, Lihua

AU - Cai, Qingsong

AU - Tang, Ming

AU - Liu, Yang

AU - Chen, Hao

AU - Reisman, David

AU - Wu, Lizi

AU - Seto, Edward

AU - Qiu, Yi

AU - Dou, Yali

AU - Casero, Robert A.

AU - Lu, Jianrong

PY - 2016/6/21

Y1 - 2016/6/21

N2 - 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.

AB - 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.

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