From: Mannervik et al. (1999) Science 284, 606-609. Multiple tiers of activation and repression. (Top) Sequence-specific activators bound to a distal enhancer recruit the CBP (CBP =CREB binding protein) coactivator. Recent studies suggest that CBP is a subunit of larger coactivator complexes (such as PCAF = p300/CBP associated factor). The complexes might mediate activation through the decondensation of chromatin at the core promoter, and by interacting with either the pol II complex or general coactivator complexes, which in turn facilitate the binding of the general transcription factors (GTFs) and pol II. (Bottom) Similarly, distal repressors recruit corepressor complexes that might also possess multiple activities. Perhaps some subunits, such as Rpd3 (a histone deacetylase), condense chromatin, whereas other subunits interact with general repressor complexes (NC2, Mot1), which in turn preclude binding of pol II.