A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform
Summary
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 singl
Content
# A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform
*Published: 2026 Apr 2*
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 isolation sequesters TFs from mSWI/SNF and poisons TF-"addicted"
cancer cells. Finally, TFs across diverse families interact with SMARCD
paralog-specific SWIFT domains. These results define a major mechanism of cell
type- and disease-specific mSWI/SNF chromatin targeting and inform approaches
toward therapeutic modulation.
DOI: 10.1126/science.aeb3627