A Coordinated Global Control over Cellular Transcription

Abstract

Although much is known about the regulation of gene transcription in eukaryotes, it is not clear whether cells have global controls that determine overall rates of transcription. We have investigated the effects that the DNA-to-protein ratio has on both total transcription and the transcription of individual genes in the unicellular eukaryote fission yeast.Mutants altered in cell size and those blocked in cell-cycle progression were used to vary the DNA-to-protein ratio over a 5-fold range. We found that cells of sizes within 2-fold of the wild-type value regulated global transcription tomaintain similar transcription rates per protein regardless of the cellular DNA content. These changes in total transcription correlated with coordinated changes in gene occupancy by RNA polymerase II. In cell-cycle-arrested mutants exceeding a certain size, total transcription rates plateaued as DNA became limiting for transcription at low DNA-to-protein ratios [1]. Unexpectedly, expression levels of individual genes remained tightly coordinated with each other over the entire range of cell sizes. We propose that there is a coordinated, global control that determines the rate of transcription of most genes and that this control plays a role in regulating growth rate of the cell.