In order to switch genes on and off, chromatin has to be opened and shut, enabling the DNA to become open to the whim of the rest of the nucleus for transcription. This is called chromatin remodelling, and it’s far from an easy task because our DNA is wrapped around huge protein complexes called nucleosomes.

Nucleosomes are vital, but they’re also a massive pain. They are large, heavy, and require considerable amounts of energy to move. One player involved in this is the SWI/SNF family of proteins — massive chromatin remodeller complexes that can boot stubborn nucleosomes out the way to allow (or prevent) transcription at specific genes.

We’ve known about SWI/SNF complexes for years, having first cloned them in the 1990s. But one outstanding question has remained: across the 2 metres of DNA folded up in each nucleus, how do they know where to go? And when? Perhaps another protein in the cell can help them do so, but it has proven difficult to find such a partnership.

Jain et al. recently identified a region of the mSWI/SNF complex — called the SWIFT domain — which binds different transcription factors. This binding essentially guides the SWI/SNF complex to where it needs to go.

The SWIFT domain liked interacting directly with a transcription factor protein called PU.1. A single amino acid mutation stopped PU.1 from binding, and the SWI/SNF complex now no longer could find its target sites on the DNA to open or close. Such direct binding between SWI/SNF and transcription factors has never been previously shown.

However, it wasn’t just PU.1 — other transcription factors were also able to bind to the SWIFT complex, which allowed the SWI/SNF complex to localise to different sequences within the DNA to drive transcription. This is little like how if you put different people in the driver’s seat of the same car and ask them to drive home, they’d all go to different places.

The authors did most of this work in cancer cells. This is because in many cancers, TFs and SWI-SNF protein expression and activity are shown to be dysregulated, but how (and whether) they physically interacted on a molecular level had not yet been shown clearly, until now.

But why bother studying these tiny interactions? TFs and SWI/SNF remodellers are vital architects of transcription — their buddying up could launch gene expression programmes within our cells that allow the cell to become resistant to chemotherapeutic drugs. Finding out how this works is crucial to our understanding of cancer biology, and may, in future, allow us to develop cell type- and disease-specific treatments.

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