Genome-wide maps of Qki-5, Srebp2, and Pol II in oligodendrocytes. Genome-wide maps of Qki-5, Srebp2, and Pol II in oligodendrocytes

We found the genome-wide co-localization of Qki-5 and Srebp2. Notably, the genomic distribution analysis revealed that Qki-5 and Srebp2 highly co-occupied the regions of the promoter/transcription start site (TSS), where active transcription was taken place in a oligodendrocyte-specific manner, which was indicated by Pol II binding events. GO analysis of the genes whose promoters were co-bound by Qki-5, Srebp2, and Pol II showed a significant enrichment of the Srebp2-mediated cholesterol biosynthesis pathway, and Qki depletion led to reduced recruitment of Srebp2 and Pol II on the promoters of the genes involved in cholesterol biosynthesis. These data suggest Qki-5 as a potential transcription co-activator of Srebp2-mediated cholesterol biosynthesis in oligodendrocytes. Overall design: Examination of genome-wide maps Qki-5, Srebp2, and Pol II in WT and Qki KO oligodendrocytes which are differentiated from neural stem cells.

我们在全基因组范围内检测到Qki-5与Srebp2的共定位现象。值得注意的是，基因组分布分析结果显示，Qki-5与Srebp2高度共占据启动子/转录起始位点（Transcription Start Site, TSS）区域；该区域的活跃转录以少突胶质细胞特异性的方式进行，这一结论可通过RNA聚合酶II（Pol II）的结合事件得到佐证。对启动子区域被Qki-5、Srebp2及Pol II共同结合的基因进行基因本体（Gene Ontology, GO）富集分析后发现，Srebp2介导的胆固醇生物合成通路呈现显著富集；而Qki敲除会导致胆固醇生物合成相关基因的启动子区域上Srebp2与Pol II的招募量显著降低。上述实验数据表明，Qki-5在少突胶质细胞中可作为Srebp2介导的胆固醇生物合成通路的潜在转录共激活因子。实验整体设计：对源自神经干细胞分化得到的野生型（Wild Type, WT）与Qki基因敲除（Knockout, KO）少突胶质细胞进行Qki-5、Srebp2及Pol II的全基因组结合图谱检测。