IUF - Leibniz Research Institute for Environmental Medicine at Heinrich-Heine University Duesseldorf, D-40225 Duesseldorf, Germany.
Nucleic Acids Res. 2011 Jun;39(11):4612-27. doi: 10.1093/nar/gkr069. Epub 2011 Feb 8.
While it is widely acknowledged that the ubiquitin-proteasome system plays an important role in transcription, little is known concerning the mechanistic basis, in particular the spatial organization of proteasome-dependent proteolysis at the transcription site. Here, we show that proteasomal activity and tetraubiquitinated proteins concentrate to nucleoplasmic microenvironments in the euchromatin. Such proteolytic domains are immobile and distinctly positioned in relation to transcriptional processes. Analysis of gene arrays and early genes in Caenorhabditis elegans embryos reveals that proteasomes and proteasomal activity are distantly located relative to transcriptionally active genes. In contrast, transcriptional inhibition generally induces local overlap of proteolytic microdomains with components of the transcription machinery and degradation of RNA polymerase II. The results establish that spatial organization of proteasomal activity differs with respect to distinct phases of the transcription cycle in at least some genes, and thus might contribute to the plasticity of gene expression in response to environmental stimuli.
虽然普遍认为泛素-蛋白酶体系统在转录中起着重要作用，但对于其机制基础，特别是在转录部位依赖蛋白酶体的蛋白水解的空间组织，知之甚少。在这里，我们表明蛋白酶体活性和四聚泛素化蛋白集中在常染色质的核质微环境中。这些蛋白水解结构域是不可移动的，并且与转录过程明显相关。对秀丽隐杆线虫胚胎中的基因芯片和早期基因的分析表明，相对于转录活跃的基因，蛋白酶体和蛋白酶体活性在空间上是远离的。相比之下，转录抑制通常会导致蛋白酶体活性的局部重叠与转录机制的组成部分，并导致 RNA 聚合酶 II 的降解。这些结果表明，蛋白酶体活性的空间组织在至少一些基因的转录周期的不同阶段是不同的，因此可能有助于基因表达对环境刺激的可塑性。
