There are three main categories for triggering the release of sigmas factors from anti-sigma factors: partner switching, direct signaling, and a mechanism regulated by proteolysis.
The partner-switching mechanism is commonly found in Gram-positive bacteria. It consists of four key players: a sigma factor, an anti-sigma factor, an anti-anti-sigma factor, and an input phosphatase complex. A cell that is not under stress has an anti-sigma factor that is bound to the sigma factor on the gene and keeps it inactive. In times of stress, a phosphatase complex dephosphorylates the anti-sigma factor, allowing the anti-sigma factor to switch partners and bind to the anti-anti-sigma factor. This frees the sigma factors to activate the gene. Environmental stressors, such as heat, often activate this mechanism.
The direct signaling mechanism is as it sounds: the anti-sigma factor binds to a signal, which causes conformation changes in the structure of the anti-sigma factors, resulting in the release of the sigma factors.
The regulated intramembrane proteolysis (RIP) mechanism allows signal transduction across membranes. This mechanism is often used to regulate ECF sigma factors. The mechanism involves two sequential cleavages, the first being an external cleavage of membrane-traversing anti-sigma factor and the second cleavage of the anti-sigma factors in the membrane's plane, resulting in a free cytoplasmic domain.