ERRα induces H3K9 demethylation by LSD1 to promote cell invasion - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2017

ERRα induces H3K9 demethylation by LSD1 to promote cell invasion

Résumé

Lysine Specific Demethylase 1 (LSD1) removes mono-and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor a (ERR alpha) display commonly activated genes. Transcriptional activation by LSD1 and ERR alpha involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERR alpha is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERR alpha coregulate several target genes involved in cell migration, including the MMP1 matrix metallo-protease, also activated through H3K9 demethylation at the TSS. Depletion of LSD1 or ERR alpha reduces the cellular capacity to invade the extracellular matrix, a phenomenon that is rescued by MMP1 reexpression. Altogether our results identify a regulatory network involving a direct switch in the biochemical activities of a histone demethylase, leading to increased cell invasion.

Dates et versions

hal-02346533 , version 1 (05-11-2019)

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Citer

Julie Carnesecchi, Christelle Forcet, Ling Zhang, Violaine Tribollet, Bruno Barenton, et al.. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 (15), pp.3909-3914. ⟨10.1073/pnas.1614664114⟩. ⟨hal-02346533⟩
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