MYC, Topoisomerase, Supercoiling and the FuBPs: Partners in the Control of Global Expression Levels (#37)
Most studies of gene regulation focus on the relative expression of different genes. However, mechanisms exist that control the transcription globally. MYC directly regulates the output of all active genes both via binding with promoter proximal E-boxes (CACGTG) and via E-box independent mechanisms. MYC-driven transcription amplification of gene expression is not uniform, but becomes most pronounced for highly expressed genes, until MYC-saturated. Because high-level transcription is associated with the generation of high-levels of opposing mechanical force (especially torque—supercoiling) we reasoned that cells must manage the generation and removal of these forces prompting us to explore the role of topoisomerases throughout the transcription cycle. Regulation of topoisomerase activity enables cells to exploit the mechanical energy of transcription to control RNA polymerase pausing and pause-release. Moreover, the genomic response to the generation of these forces leads to a plethora of non-B DNA structures replete with regulatory potential such as we find at the Far Upstream element of MYC.