The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1.
Epithelial-mesenchymal transition (EMT) is a transdifferentiation programme. The mechanism underlying the epigenetic regulation of EMT remains unclear. In this study, we identified that Snail1 interacted with histone lysine-specific demethylase 1 (LSD1). We demonstrated that the SNAG domain of Snail1 and the amine oxidase domain of LSD1 were required for their mutual interaction. Interestingly, the sequence of the SNAG domain is similar to that of the histone H3 tail, and the interaction of Snail1 with LSD1 can be blocked by LSD1 enzymatic inhibitors and a histone H3 peptide. We found that the formation of a Snail1-LSD1-CoREST ternary complex was critical for the stability and function of these proteins. The co-expression of these molecules was found in cancer cell lines and breast tumour specimens. Furthermore, we showed that the SNAG domain of Snail1 was critical for recruiting LSD1 to its target gene promoters and resulted in suppression of cell migration and invasion. Our study suggests that the SNAG domain of Snail1 resembles a histone H3-like structure and functions as a molecular hook for recruiting LSD1 to repress gene expression in metastasis.
Lin
Yiwei
Y
Departments of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA.
Wu
Yadi
Y
Li
Junlin
J
Dong
Chenfang
C
Ye
Xiaofeng
X
Chi
Young-In
YI
Evers
B Mark
BM
Zhou
Binhua P
BP
D000818:Animals; D002454:Cell Differentiation; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*
D006657:Histones; D010455:Peptides; D008995:Monoamine Oxidase; D008239:Lysine
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