Identification of Enhancers and Promoters in the Genome by Multidimensional Scaling

Abstract

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.