ERRα induces H3K9 demethylation by LSD1 to promote cell invasion
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. W...
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| Main Author: | |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 11, 2017
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| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2017, Volume: 114, Issue: 15, Pages: 3909-3914 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1614664114 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1073/pnas.1614664114 Verlag, Volltext: http://www.pnas.org/content/114/15/3909 
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| Author Notes: | Julie Carnesecchi, Christelle Forcet, Ling Zhang, Violaine Tribollet, Bruno Barenton, Rafik Boudra, Catherine Cerutti, Isabelle M. L. Billas, Aurélien A. Sérandour, Jason S. Carroll, Claude Beaudoin, Jean-Marc Vanacker |
| Summary: | 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 α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERRα is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERRα 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 ERRα 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. |
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| Item Description: | Gesehen am 25.04.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1614664114 |