Fluctuations in the initiation rate of transcription, the first step in gene expression, ensue from the stochastic behavior of the molecular process that controls transcription. In steady state, the regulatory process is often assumed to operate reversibly, i.e., in equilibrium. However, reversibility imposes fundamental limits to information processing. For instance, the assumption of equilibrium is difficult to square with the precision with which the regulatory process executes its task in eukaryotes. Here we provide evidence — from microscopic analyses of the transcription dynamics at a single gene copy of yeast — that the regulatory process for transcription is cyclic and irreversible (out of equilibrium). The necessary coupling to reservoirs of free energy occurs via sequence-specific transcriptional activators and the recruitment, in part, of ATP-dependent chromatin remodelers. Our findings may help explain how eukaryotic cells reconcile the dual but opposing requirements for fast regulatory kinetics and high regulatory specificity.

转录起始速率的波动是基因表达的第一步，是由控制转录的分子过程的随机行为引起的。在稳定状态下，调节过程通常被认为是可逆的，即处于平衡状态。然而，可逆性对信息处理施加了根本限制。例如，平衡的假设很难与真核生物中调节过程执行其任务的精确度相符。在这里，我们通过对酵母单个基因拷贝的转录动力学的微观分析提供了证据，证明转录的调控过程是循环的且不可逆的（不平衡）。与自由能储存库的必要耦合是通过序列特异性转录激活剂和部分 ATP 依赖性染色质重塑剂的招募而发生的。我们的发现可能有助于解释真核细胞如何调和快速调节动力学和高调节特异性的双重但相反的要求。