The SNAG domain of snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1

Yiwei Lin, Yadi Wu, Junlin Li, Chenfang Dong, Xiaofeng Ye, Young In Chi, B. Mark Evers, Binhua P. Zhou

Research output: Contribution to journalArticlepeer-review

290 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1803-1816
Number of pages14
JournalEMBO Journal
Volume29
Issue number11
DOIs
StatePublished - Jun 2 2010

Funding

FundersFunder number
National Childhood Cancer Registry – National Cancer InstituteR01CA125454

    Keywords

    • Chromatin
    • Demethylation
    • EMT
    • LSD1
    • Snail1

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • General Biochemistry, Genetics and Molecular Biology
    • General Immunology and Microbiology

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