How do you label a protein that you may want to un-label a few seconds later? That question runs through Turning Fluorescence On and Off: Reversible Tags for Live-cell Imaging, an article by Luc Lenglet of The Twinkle Factory, published by Labcompare on 11 September 2026.
Fluorescent proteins and self-labeling enzyme tags such as SNAP-tag and HaloTag share one trait: once the label is on, it stays on. The article walks through a different family of reporters, in which a small TFFluorogen stays dark in solution and lights up only while it sits in the pocket of its protein partner. Because binding is non-covalent, the signal goes off when the TFFluorogen is washed out and comes back when it is added again.
Three tools are covered:
- FAST, a 14 kDa tag that needs no oxygen and labels almost instantly, which has made it a workhorse in strict anaerobes;
- splitFAST, a split reporter whose signal follows protein-protein interactions as they form and dissolve, within seconds;
- CATCHFIRE, a chemically induced dimerization system in which the molecule that brings two proteins together is also the one that makes them glow.
The article does not argue that one approach should replace the others. It shows where reversible, low-background chemistry fits alongside established tags, with a 2020 study that combined FAST, HaloTag and SNAP-tag in the same anaerobic bacterium, and it closes on the de novo designed NovoTags reported in Science in July 2026.
Read the full article on Labcompare → For a side-by-side comparison of the four technologies, see FAST vs GFP, HaloTag® and SNAP-tag; to switch a signal off and on at will, see reversible labeling.
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