A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform

Jain, Siddhant U.; Williamson, Kaylyn E.; Ying, Alexander W.; Turner, Aasha M.; Jiang, Ruidong; Raval, Shaunak; So, Kevin; Allison, Maxwell J.; Sankar, Akshay; Guerra, Daniel D. Samé; Lin, Yutong; Jiang, Zhe; Mashtalir, Nazar; Rohrs, Henry W.; Lichti, Cheryl F.; Muir, Tom W.; Papanastasiou, Malvina; Paulo, João A.; Gygi, Steven P.; Gross, Michael L.; Kadoch, Cigall

doi:10.1126/science.aeb3627

articleScienceJan 1, 2026HYBRID OA

A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform

SUSiddhant U. Jain KEKaylyn E. Williamson AWAlexander W. Ying AMAasha M. Turner RJRuidong Jiang

Harvard University · Dana-Farber Cancer Institute · +4 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Mammalian switch/sucrose nonfermenting (mSWI/SNF) chromatin remodeling complexes modulate DNA accessibility and gene expression; however, their genomic targeting mechanisms remain incompletely understood. Here, we identify SWIFT [SWI/SNF immunoglobulin fold (Ig-fold) for transcription factor interactions], a conserved transcription factor (TF) binding domain on the SMARCD subunits. SWIFT is necessary and sufficient for direct engagement with the transactivation domain of the PU.1 TF. A single amino acid mutation disrupts PU.1-mSWI/SNF binding, impairs complex targeting, and attenuates oncogenic transcription and proliferation in PU.1-dependent human cancer cells. Dominant expression of the SWIFT domain in…

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Topics & keywords

Topics

Keywords

Transcription factor
Transactivation
Chromatin
Transcription (linguistics)
Gene
DNA-binding domain
Chromatin remodeling
Chromatin immunoprecipitation

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