Cells can control gene expression by winding their DNA around proteins to create disks called nucleosomes. The condensed DNA, known as repressed chromatin, can’t be transcribed, so its genes are effectively turned off. HHMI investigator Bradley Cairns recently discovered how one of the molecular machines that assembles chromatin knows when to work.
Cairns and Cedric Clapier, at the University of Utah School of Medicine, focused on a complex called an assembly remodeler, which moves nucleosomes close together. The remodeler has an internal motor that winds DNA around the nucleosome, but scientists struggled to understand how this motor was turned on and regulated. Cairns and Clapier discovered that the nucleosome activates the motor by flipping a “switch” adjacent to it. As they reported December 13, 2012, in Nature, this mechanism ensures that the motor operates only when the remodeler is bound to the right nucleosome.
Cairns believes this switch is a universal toggle for remodelers. “I think we will find that all remodelers have motors flanked by specialized switches specific for that particular remodeler,” he says. Cairns hopes to substantiate that idea by looking for switches on disassembly remodelers, protein complexes that eject nucleosomes from DNA to promote transcription.