Global repression of mesenchymal genes in epithelial cells by the histone demethylase LSD1

In HCT116 epithelial cells, LSD1 binds primed mesenchymal promoters and its ablation rapidly derepresses SNAI2 and ZEB1, while E-cadherin remains repressed.

• Why it matters: EMT is driven by SNAI, ZEB, and TWIST factors via LSD1, but conflicting reports suggest LSD1 inhibition can increase mesenchymal markers in epithelial contexts.
• What they did: The study mapped genome-wide LSD1 binding in HCT116 cells and used rapid degron-mediated ablation of endogenous LSD1 to measure nascent and steady-state transcription and chromatin accessibility.
• The result: LSD1 ablation activates SNAI2 and ZEB1 and represses epithelial hallmarks like E-cadherin; re-introducing LSD1 downregulates SNAI2 and ZEB1 yet further represses E-cadherin, questioning LSD1 inhibition for EMT control.

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