Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA.
J Cell Biol. 2021 Sep 6;220(9). doi: 10.1083/jcb.202009197. Epub 2021 Jun 15.
While much is known about how transcription is controlled at individual genes, comparatively little is known about how cells regulate gene expression on a genome-wide level. Here, we identify a molecular pathway in the C. elegans germline that controls transcription globally in response to nutritional stress. We report that when embryos hatch into L1 larvae, they sense the nutritional status of their environment, and if food is unavailable, they repress gene expression via a global chromatin compaction (GCC) pathway. GCC is triggered by the energy-sensing kinase AMPK and is mediated by a novel mechanism that involves the topoisomerase II/condensin II axis acting upstream of heterochromatin assembly. When the GCC pathway is inactivated, then transcription persists during starvation. These results define a new mode of whole-genome control of transcription.
尽管人们对单个基因的转录调控了解较多,但对细胞如何在全基因组水平上调控基因表达却知之甚少。在这里,我们鉴定了线虫生殖系中一种分子途径,该途径可响应营养胁迫全局调控转录。我们报告说,当胚胎孵化成 L1 幼虫时,它们会感知周围环境的营养状况,如果没有食物,它们会通过全局染色质紧缩(GCC)途径抑制基因表达。GCC 是由能量感应激酶 AMPK 触发的,并通过一种涉及拓扑异构酶 II/凝聚素 II 轴的新型机制介导,该机制作用于异染色质组装的上游。当 GCC 途径失活时,那么在饥饿期间转录仍会持续。这些结果定义了一种新的全基因组转录调控模式。