In recent years, physical elements of transcription have emerged as central in our understanding of gene expression. Recent work has been done introducing a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase (RNAP) rotation and DNA supercoiling are coupled (1). Here we generalize this framework to accommodate the behavior of many RNAPs operating on multiple genes on a shared piece of DNA. The resulting framework is combined with well-established stochastic processes of transcription resulting in a model which characterizes the impact of the mechanical properties of transcription on gene expression and DNA structure. Transcriptional bursting readily emerges as a common phenomenon with origins in the geometric nature of the genetic system and results in the bounding of gene expression statistics. Properties of a multiple gene system are examined with special attention paid to the role that genome composition (gene orientation, size and intergenic distance) plays in the ability of genes to transcribe. The role of transcription in shaping DNA structure is examined and the possibility of transcription driven domain formation is discussed.
Over the past several decades it has been increasingly recognized that stochastic processes play a central role in transcription. Although many stochastic effects have been explained, the source of transcriptional bursting (one of the most well-known sources of stochasticity) has continued to evade understanding. Recent results have pointed to mechanical feedback as the source of transcriptional bursting, but a reconciliation of this perspective with preexisting views of transcriptional regulation is lacking. In this article, we present a simple phenomenological model that is able to incorporate the traditional view of gene expression within a framework with mechanical limits to transcription. By introducing a simple competition between mechanical arrest and relaxation copy number probability distributions collapse onto a shared universal curve under shifting and rescaling and a lower limit of intrinsic noise for any mean expression level is found.transcription | supercoiling | topoisomerase | bursting noise T he ability to watch biological phenomena play out at the single-molecule level has revealed a rich and nuanced view of the central dogma of biology. From the single-molecule vantage it has become clear that random forces and events play a key role in transcription (1), although how important expression noise is for crucial biological functions is a matter of debate. The identification of transcriptional bursting, in which genes undergo periods of paused activity even in fully induced environments in both prokaryotes and eukaryotes (2, 3), has been one of the most notable examples of this new perspective. Bursting has also figured prominently in the discussion concerning universal properties of transcriptional noise (4). In particular, a number of recent experimental results have found a link between the rate and randomness of mRNA production whereby highly expressed genes have increased noise associated with production (4). This result transcends specific organisms or genes and may be explained if expression inevitably exhibits bursting. Other work, however, has argued that under some conditions there are nonuniversal gene-specific relationships between the rate and randomness of mRNA production (5); these results are more consistent with the pure model of transcription regulated by the binding of specific regulatory proteins to the promoter regions, in which high expression is not necessarily associated with high noise.What is needed is a framework that is able to accommodate the traditional "promoter architecture" view of transcription while at the same time capturing recently observed universal aspects of bursting. To accomplish this, we start from the "twin-supercoiling domain" (6) model of transcription wherein the helical nature of DNA combined with topological obstructions leads to the accumulation of mechanical strain in DNA during transcription. This strain can result in arrested gene expression. Specific biological machinery (topoisomerases) must relieve the strain created by transcription throug...
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