The Role of Promoter DNA Topology In Actively Transcribing Genes

Dramatic changes in promoter DNA topology have so far been associated with the repressed chromatin state when the DNA is wrapped around the histone octamer of the nucleosome core particle—the building block of higher order chromatin structures. Two master transcriptional regulators: TFIID and SAGA are both mega-Dalton complexes that deliver regulatory DNA binding proteins to the core promoters of genes. Both TFIID and SAGA contain a set of histone-like proteins. The role of those proteins in these two master transcriptional regulators is not understood. We have obtained preliminary evidence that dramatic changes in promoter DNA topology are not exclusive to the repressed chromatin state but play an important role in initiation of transcription. We propose that a substantial rearrangement of the DNA topology of actively transcribing genes is required for the assembly of a pre-initiation complex capable of selecting the correct transcription start site.