Dual Regulation of Transcription Factor Binding by Tup11/12-Mediated Destabilization and DNA Loop-Mediated Stabilization Ensures Stress-Specific Gene Activation in Fission Yeast

Moreover, this aberrant fbp1 activation is diminished by the loss of Php5, a factor indispensable for DNA-loop formation between Atf1- and Rst2-binding sites. The defective nonspecific transcription in the tup11∆/tup12∆/php5∆ mutant is restored when Atf1- and Rst2-binding sites are artificially positioned in proximity to each other, indicating that reciprocal stabilization between these TFs facilitates their binding. These findings demonstrate that fbp1 achieves stress-specific transcriptional activation through the counteractive regulation of TF-binding: Tup11/12-mediated destabilization and DNA loop-mediated stabilization.

The synergistic reduction in stress tolerance observed in the tup11∆/tup12∆/php5∆ mutant further suggests that this dual regulatory mechanism is crucial for cellular adaptation to environmental stresses.