Figure 2

Schematic of a general model for the silencing of CIITA transcription in trophoblasts. The CIITA PIV is associated with HDACs (red circles) in CIITA-inducible cells and trophoblasts in the absence of IFN-γ, which helps to maintain a closed chromatin conformation (represented as blackened bars). IRF-2 may or may not be bound constitutively to the CIITA PIV in CIITA-inducible cells. Following exposure of the cells to IFN-γ, STAT-1 (blue rectangle) is phosphorylated (represented by the red dot), and subsequently dimerizes, translocates to the nucleus, and induces synthesis of IRF-1 (yellow ovals), but the levels of these factors are higher in CIITA-inducible cells relative to trophoblasts. STAT-1 and IRF-1 bind to their respective elements at the PIV in CIITA-inducible cells, and recruit HATs (light green circles) to the promoter. This leads to changes in the chromatin to an open conformation (light gray bars) and initiation of transcription. In contrast, this sequence of events does not occur in trophoblasts, and the chromatin remains in a closed conformation.