Genome-wide maps of QKI-5, SREBP2, and POL II in eye lens cells

We found the genome-wide co-binding of QKI-5 and SREBP2. Notably, the genomic distribution analysis revealed that the co-binding events between QKI-5 and SREBP2 highly occurred at the regions of the promoter/transcription start site (TSS), where active transcription was taken place in a lens cell-specific manner, which was indicated by POL II binding events. Cellular pathway analysis of the genes whose promoters were co-bound by QKI-5, SREBP2, and POL II showed a significant enrichment of the SREBP2-medaited cholesterol biosynthesis pathway, and QKI depletion led to reduced co-occupancies 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 mediating SREBP2-dependent cholesterol biosynthesis in eye lens cells.

我们检测到QKI-5与SREBP2在全基因组范围内的共结合现象。值得注意的是，基因组分布分析显示，QKI-5与SREBP2的共结合事件高度富集于启动子/转录起始位点（transcription start site，TSS）区域；该区域以晶状体细胞特异性的方式开展活跃转录，这一现象可由RNA聚合酶II（POL II）的结合事件所证实。对启动子区域被QKI-5、SREBP2与POL II共同结合的基因进行细胞通路富集分析，结果显示其显著富集于SREBP2介导的胆固醇生物合成通路；且QKI敲低会使SREBP2与POL II在胆固醇生物合成相关基因启动子上的共占据水平显著降低。上述研究数据表明，QKI-5是一种潜在的转录共激活因子，可在眼晶状体细胞中介导SREBP2依赖的胆固醇生物合成过程。