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© Research
Publication : EMBO reports

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in EMBO reports - 05 Jul 2021

Jarroux J, Foretek D, Bertrand C, Gabriel M, Szachnowski U, Saci Z, Guo S, Londoño-Vallejo A, Pinskaya M, Morillon A,

Link to Pubmed [PMID] – 33960111

Link to DOI – 10.15252/embr.202050193

EMBO Rep 2021 07; 22(7): e50193

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.

https://pubmed.ncbi.nlm.nih.gov/33960111