Programmable Histone Acetylation Enables Reversible Regulation of Cellulase Production in Myceliophthora thermophila

The dependence of these effects on guide RNA-directed targeting and p300 catalytic activity was confirmed using no-guide controls and the selective p300 inhibitor A-485. We further developed an inducible dCas9-p300 system to examine the persistence and reversibility of the activated state. Following inducer withdrawal, the high cellulase-production phenotype was maintained during the initial propagation but gradually declined over successive passages and was restored upon re-induction.

These results demonstrate that targeted histone acetylation can coordinately activate an endogenous cellulolytic regulatory network and establish a reversible high-production state without altering the DNA sequences of the target loci. This work provides a chromatin-39 based strategy for reversible regulation of endogenous gene networks and protein production in filamentous fungi.