Genomic association of the proteasome demonstrates overlapping gene regulatory activity with transcription factor substrates
Genomic association of the proteasome demonstrates overlapping gene regulatory activity with transcription factor substrates
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DOI：
10.1016/j.molcel.2006.02.020
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发表时间：
2006-03-17
期刊：
影响因子：
16
通讯作者：
Silver, PA
中科院分区：
文献类型：
--
作者：
Auld, KL;Brown, CR;Silver, PA
蛋白酶体可以通过对转录因子的蛋白水解和基因位点的结合来调节转录，但目前还没有发现蛋白酶体调控的靶点。使用全基因组定位分析和转录谱在酿酒酵母中，我们已经建立了哪些基因的蛋白酶体和Spt 23和Mga 2，转录因子激活的蛋白酶体的约束和调节。我们观察到蛋白酶体与高度转录的基因组相关，受交配型基因座控制，并参与脂质代谢。在核糖体蛋白（RP）基因，蛋白酶体和RNA聚合酶II（RNA Pol II）结合富集在蛋白酶体突变体，表明蛋白酶体在解离延伸复合物的作用。Spt 23和Mga 2的基因组定位与蛋白酶体结合基因有明显重叠。最后，蛋白酶体以两种不同的方式起作用，一种依赖于Spt 23/Mga 2切割，另一种独立于Spt 23/Mga 2切割，这为蛋白酶体及其底物的协同基因调控提供了证据。
The proteasome can regulate transcription through proteolytic processing of transcription factors and via gene locus binding, but few targets of proteasomal regulation have been identified. Using genome-wide location analysis and transcriptional profiling in Saccharomyces cerevisiae, we have established which genes are bound and regulated by the proteasome and by Spt23 and Mga2, transcription factors activated by the proteasome. We observed proteasome association with gene sets that are highly transcribed, controlled by the mating type loci, and involved in lipid metabolism. At ribosomal protein (RP) genes, proteasome and RNA polymerase II (RNA Pol II) binding was enriched in a proteasome mutant, indicating a role for the proteasome in dissociating elongation complexes. The genomic occupancies of Spt23 and Mga2 overlapped significantly with the genes bound by the proteasome. Finally, the proteasome acts in two distinct ways, one dependent and one independent of Spt23/Mga2 cleavage, providing evidence for cooperative gene regulation by the proteasome and its substrates.