Identification of a Distal Enhancer That Regulates TGF‐β–Induced SNAI1 Expression

• DOI: 10.1111/cas.70091
• Publication Date: 2025-05-14T06:40:15Z
• Authors: Hao Fu; Yuka Itoh; Tomoe Sawaguchi; Shigeo Otake; Chiho Omata; Masao Saitoh; Keiji Miyazawa
• Keywords: SNAI1; Enhancer RNAs

ABSTRACT Snail is a zinc finger transcription factor encoded by the SNAI1 gene and triggers cellular process termed epithelial‐mesenchymal transition (EMT) upon its increased expression and/or functional activation. activity are regulated various extracellular stimuli, including cytokines environmental factors. Transforming growth factor‐β (TGF‐β) inducer that functions via Smad3‐mediated transcriptional In present study, we identified distal enhancer modulates TGF‐β–induced expression. ChIP‐seq Hi‐C analyses showed located 46 kb downstream of gene; in TGF‐β–stimulated cells, it associates with Smad3 interacts proximal promoter. Inhibiting using CRISPRi attenuated expression, stress fiber formation, cell motility enhancement, suggesting mediates EMT. The contains Smad‐binding CAGA motif an activator protein‐1 (AP‐1) binding function Ras‐responsive element protein 1 (RREB1), required for basal but not inducibility TGF‐β. contrast to enhancer, association promoter was evident. These findings suggest respond distinct signaling cues, integrate them, cooperatively drive