Graduate School of Science and Engineering, Chuo University, Tokyo 112-8551, Japan.
Department of Physics, Chuo University, Tokyo 112-8551, Japan.
Genes (Basel). 2021 Oct 23;12(11):1671. doi: 10.3390/genes12111671.
The positions of enhancers and promoters on genomic DNA remain poorly understood. Chromosomes cannot be observed during the cell division cycle because the genome forms a chromatin structure and spreads within the nucleus. However, high-throughput chromosome conformation capture (Hi-C) measures the physical interactions of genomes. In previous studies, DNA extrusion loops were directly derived from Hi-C heat maps. Multidimensional Scaling (MDS) is used in this assessment to more precisely locate enhancers and promoters. MDS is a multivariate analysis method that reproduces the original coordinates from the distance matrix between elements. We used Hi-C data of cultured osteosarcoma cells and applied MDS as the distance matrix of the genome. In addition, we selected columns 2 and 3 of the orthogonal matrix U as the desired structure. Overall, the DNA loops from the reconstructed genome structure contained bioprocesses involved in transcription, such as the pre-transcriptional initiation complex and RNA polymerase II initiation complex, and transcription factors involved in cancer, such as Foxm1 and CREB3. Therefore, our results are consistent with the biological findings. Our method is suitable for identifying enhancers and promoters in the genome.
增强子和启动子在基因组 DNA 上的位置仍然知之甚少。由于基因组形成染色质结构并在核内展开，因此在细胞分裂周期中无法观察到染色体。然而，高通量染色体构象捕获（Hi-C）可测量基因组的物理相互作用。在以前的研究中，DNA 挤出环直接从 Hi-C 热图中得出。多维尺度分析（MDS）在此评估中用于更准确地定位增强子和启动子。MDS 是一种多元分析方法，可从元素之间的距离矩阵中再现原始坐标。我们使用培养骨肉瘤细胞的 Hi-C 数据，并将 MDS 用作基因组的距离矩阵。此外，我们选择正交矩阵 U 的第 2 列和第 3 列作为所需的结构。总的来说，从重建的基因组结构中得到的 DNA 环包含参与转录的生物过程，例如转录起始复合物和 RNA 聚合酶 II 起始复合物，以及参与癌症的转录因子，如 Foxm1 和 CREB3。因此，我们的结果与生物学发现一致。我们的方法适用于识别基因组中的增强子和启动子。
