Figure 8. Models for transcriptional memory.
(A) Set1/COMPASS remodeling during INO1 transcriptional memory. Nucleosomes associated with repressed INO1 in the nucleoplasm are hypoacetylated and unmethylated. Active INO1 is targeted to the nuclear periphery, nucleosomes are acetylated (orange circles) and H3K4 is trimethylated (blue circles) by COMPASS. During memory, INO1 remains associated with the nuclear pore complex, acetylation is lost, H2A.Z is incorporated and H3K4 is dimethylated by a remodeled form of COMPASS lacking the Spp1 subunit (purple). H3K4me2 recruits Set3C, which promotes the persistence of H3K4me2 by feedback on COMPASS recruitment or remodeling. (B) Cdk8+ Mediator promotes transcriptional poising. Upon activation, Cdk8- Mediator and the PIC bind to the INO1 promoter. TFIIK (Kin28/Cdk7) phosphorylates Serine 5 on the carboxy terminal domain of RNAPII to initiate transcription. During memory, Kin28 is lost and Cdk8+ Mediator is recruited. Cdk8+ Mediator promotes PIC recruitment but initiation is blocked by the absence of Kin28, poising the promoter for future activation.