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Updated: Aug 29, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Regulation of large-scale chromatin unfolding by Smad4
Jinghua Yan1, Yan Fang, Lihua Ding
1Beijing Institute of Biotechnology, Beijing 100850, PR China. yeqn@nic.bmi.ac.cn
Abstract:
The tumor suppressor Smad4 plays a critical role in the transforming growth factor-beta (TGF-beta signaling pathway. Smad4 is an essential component of transcriptional complexes mediating the activation of Smad-dependent target genes. However, how Smad4 regulates various chromosomal events remains unknown. Here, we report that Smad4 induces large-scale chromatin unfolding by targeting Smad4 to an amplified, lac operator-containing chromosome region in mammalian cells. This unfolding activity maps to the subdomains within the transactivation domain of Smad4. Both the N-terminal missense and the C-terminal truncated tumor-derived mutations increased the chromatin unfolding activity of Smad4. These data identify a novel function of Smad4 and suggest that regulation of large-scale chromatin unfolding by Smad4 may be responsible for cancer development.
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