Figure 1.
Proposed models for epigenetic long-term silencing of a gene. A. Active transcription of a gene is dependent on transcription factor (TF) binding. Upon removal of the TF through down-regulation, gene silencing or other means, down-regulation of the targeted gene occurs. In the absence of activating transcription factors, PcGs, HDACs, and DNMTs are recruited to the promoter and initiate long-term transcriptional repression. CpG sites adjacent to the promoter are then methylated (represented by filled circles) and eventually a heterochromatin state of long-term silencing is established. B. As in panel A transcription of a gene is dependent upon TF binding. In the absence of TF binding, PcG is recruited to a promoter and initiates long-term transcriptional repression through modification of histones. This can occur in the absence of CpG islands or methylation.