Figure 1.

A model for regulation of the GAL cluster by GAL lncRNA R-loops and Dbp2. (A) Glucose Repression When glucose is available, Dbp2 is localized in the nucleus⁷⁴ and prevents the accumulation of R-loops at the GAL gene cluster⁵³ via the assembly of Dbp2-dependent lncRNA-protein complexes.⁵⁶ This allows the successful docking of the Cyc8/Tup1 co-repressor complex and subsequent repression. (B) Carbon Source Switch During a switch from glucose to galactose, Dbp2 is actively relocalized to the cytoplasm via export through the nuclear pore complex (NPC).⁷⁴ This may alter lncRNP assembly and cause R-loop formation and spreading across the GAL cluster. R-loop formation likely interferes with binding of transcriptional repressors and the Cyc8/Tup1 corepressor complex, causing derepression of the GAL genes. (C) Galactose Induction In the presence of galactose, the Gal4 transcriptional activator is released from the Gal80 inhibitor (not pictured),⁹⁶ enabling recruitment of co-activators and RNA P II.⁹⁷ This results in altered chromatin structure, as evidenced by looping of the GAL10 promoter and terminator,⁵³ which may enhance transcriptional induction. It is currently unknown how the GAL lncRNAs are cleared from chromatin or how Dbp2 is re-imported following long-term growth in galactose.