Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Mol Cell Biol. 2011 Jan;31(1):190-202. doi: 10.1128/MCB.00317-10. Epub 2010 Oct 18.
Eukaryotic genes respond to their environment by changing the expression of selected genes. The question we address here is whether distinct transcriptional responses to different environmental signals elicit distinct modes of assembly of the transcription machinery. In particular, we examine transcription complex assembly by the stress-directed SAGA complex versus the housekeeping assembly factor TFIID. We focus on genomic responses to the DNA damaging agent methyl methanesulfonate (MMS) in comparison to responses to acute heat shock, looking at changes in genome-wide factor occupancy measured by chromatin immunoprecipitation-microchip (ChIP-chip) and ChIP-sequencing analyses. Our data suggest that MMS-induced genes undergo transcription complex assembly sequentially, first involving SAGA and then involving a slower TFIID recruitment, whereas heat shock genes utilize the SAGA and TFIID pathways rapidly and in parallel. Also Crt1, the repressor of model MMS-inducible ribonucleotide reductase genes, was found not to play a wider role in repression of DNA damage-inducible genes. Taken together, our findings reveal a distinct involvement of gene and chromatin regulatory factors in response to DNA damage versus heat shock and suggest different implementations of the SAGA and TFIID assembly pathways that may depend upon whether a sustained or transient change in gene expression ensues.
真核基因通过改变特定基因的表达来响应其环境。我们在这里要解决的问题是,对不同环境信号的不同转录反应是否会引发转录机制的不同组装模式。具体而言,我们研究了应激导向的 SAGA 复合物与管家组装因子 TFIID 对转录复合物的组装。我们将 DNA 损伤剂甲基甲磺酸(MMS)引起的基因组反应与急性热休克的反应进行了比较,通过染色质免疫沉淀微芯片(ChIP-chip)和 ChIP-seq 分析来研究全基因组因子占有率的变化。我们的数据表明,MMS 诱导的基因依次进行转录复合物的组装,首先涉及 SAGA,然后涉及较慢的 TFIID 募集,而热休克基因则快速且平行地利用 SAGA 和 TFIID 途径。此外,我们还发现模型 MMS 诱导的核核苷酸还原酶基因的抑制剂 Crt1 并不在抑制 DNA 损伤诱导基因的表达方面发挥更广泛的作用。总之,我们的发现揭示了基因和染色质调节因子在应对 DNA 损伤与热休克时的明显参与,并表明 SAGA 和 TFIID 组装途径的不同实现方式可能取决于是否需要持续或短暂的基因表达变化。