HOTAIR lncRNA promotes epithelial-mesenchymal transition by redistributing LSD1 at regulatory chromatin regions.

Autor: Jarroux J; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France., Foretek D; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France., Bertrand C; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France., Gabriel M; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France., Szachnowski U; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France., Saci Z; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France., Guo S; Ionis Pharmaceuticals, Inc, Carlsbad, CA, USA., Londoño-Vallejo A; Telomeres and Cancer, CNRS UMR3244, Sorbonne Université, PSL Université, Institut Curie, Centre de Recherche, Paris, France., Pinskaya M; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France., Morillon A; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, France.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2021 Jul 05; Vol. 22 (7), pp. e50193. Date of Electronic Publication: 2021 May 06.
DOI: 10.15252/embr.202050193
Abstrakt: Epithelial-to-mesenchymal transition (EMT) describes the loss of epithelial traits and gain of mesenchymal traits by normal cells during development and by neoplastic cells during cancer metastasis. The long noncoding RNA HOTAIR triggers EMT, in part by serving as a scaffold for PRC2 and thus promoting repressive histone H3K27 methylation. In addition to PRC2, HOTAIR interacts with the LSD1 lysine demethylase, an epigenetic regulator of cell fate during development and differentiation, but little is known about the role of LSD1 in HOTAIR function during EMT. Here, we show that HOTAIR requires its LSD1-interacting domain, but not its PRC2-interacting domain, to promote the migration of epithelial cells. This activity is suppressed by LSD1 overexpression. LSD1-HOTAIR interactions induce partial reprogramming of the epithelial transcriptome altering LSD1 distribution at promoter and enhancer regions. Thus, we uncover an unexpected role of HOTAIR in EMT as an LSD1 decommissioning factor, counteracting its activity in the control of epithelial identity.
(© 2021 The Authors.)
Databáze: MEDLINE
Externí odkaz: