FIGURE 3.

Dual models for FACT-mediated nucleosome reorganization. The dimer eviction model proceeds through the schematic in steps 1a, 2a, and 3a. In step 1a, the FACT complex binds to the nucleosome, which is thought to be dependent upon the acidic CTD of Spt16 (13) and the N-terminal tails of the core histones (7). Next (step 2a), the FACT complex binds and evicts a single H2A-H2B dimer, creating a hexasome structure. The last step (step 3a) reinserts the evicted H2A-H2B dimer (after the cellular machinery has performed the necessary function, i.e. transcription, replication, or DNA repair) to restore a complete nucleosome. The global accessibility/non-eviction model progresses through steps 1b, 2b, and 3b. This model is also shown using yFACT, which utilizes numerous copies of Nhp6 to recognize and bind nucleosomes in the first step (step 1b) (18). In step 2b, the ySpt16-Pob3 complex is then recruited to the Nhp6-bound nucleosome, and binding induces gross conformational changes and accessibility within the nucleosome but without H2A-H2B dimer eviction (7). The H2A-H2B dimer remains tethered to the nucleosome via FACT, which facilitates reinsertion after relevant cellular processes have concluded (step 3b). Although the latter model utilizes yFACT, the overall mechanism driving global accessibility without dimer eviction could also be applicable to metazoan forms of FACT.