Widespread and precise epigenomic reprogramming in response to heat shock

Gene expression is controlled by a variety of proteins (the epigenome) whose precise organization and mechanism of action at every promoter remains to be worked out. Here we examine a functionally diverse subset of these proteins: RSC (Rsc9), SAGA (Spt3), Hsf1, general transcription factors (GTFs), FACT (Spt16), and RNA polymerase (Pol) II, under normal and acute heat shock conditions, using the ultra-high resolution genome-wide ChIP-exo assay. Our findings indicate that canonically organized proteins reside at most genes and are rapidly reorganized upon heat shock. This includes association of SAGA with Hsf1 at upstream promoters regions, RSC movement from gene bodies to promoters, and Pol II accumulation at pre-existing melted promoter DNA. Surprisingly, most of these events are not coupled to changes in gene expression. In contrast, GTF occupancy tracks with gene expression level. Together, these findings reveal that the epigenome is reprogrammed by signaling events far beyond what is indicated by gene expression changes.基因表达受多种蛋白质（表观基因组，epigenome）调控，然而这些蛋白质在每个启动子处的精确组织与作用机制仍有待阐明。本研究采用超高分辨率全基因组ChIP-exo检测技术，在正常及急性热激条件下，对其中功能多样的蛋白质子集展开研究，涉及的蛋白质包括RSC（Rsc9）、SAGA（Spt3）、Hsf1、通用转录因子（general transcription factors, GTFs）、FACT（Spt16）以及RNA聚合酶II（RNA polymerase, Pol II）。研究结果显示，以经典方式组织的蛋白质存在于大多数基因中，并会在热激条件下快速发生重排。这包括SAGA与Hsf1在启动子上游区域的结合、RSC从基因体向启动子的移动，以及RNA聚合酶II在预先解旋的启动子DNA处的聚集。令人意外的是，此类事件大多与基因表达变化并无关联。与之相反，通用转录因子的结合占据水平与基因表达水平相一致。综合以上发现，本研究表明表观基因组会被信号事件重编程，其重编程程度远超出基因表达变化所反映的范围。