Spatial Architecture of Chromatin at Loci of Tumor Suppressors and Oncogene

Abstract

The spatial organization of chromatin plays an important role in regulation of gene expression and in nuclear function. Methods such as high-throughput chromosome conformation capture (Hi-C) can quantify pairwise interaction frequencies among genomic loci and has provided a wealth of information on nuclear organization. Recent work based on the CHROMATIX method and deep sampling has allowed generation of large ensembles of 3D single-cell chromatin conformations. Though only considering physical excluded volume from cell nucleus confinement and sparse driver interactions inferred from Hi-C measurements, these 3D ensembles of single-cell chromatin conformations allow us to examine details of spatial organization of genomic loci. Here, we study how chromosomal architecture of loci containing tumor suppressor genes (TSG) and oncogenes differ between cancer cells and normal cells. We use publicly available Hi-C data from myelogenous leukemia cancer cells K562 and normal lymphoblastoid cells GM12878, and determine how 3D specific interactions, A/B compartment status, as well as linear epigenetic information differ between cancer and normal cells. We show results from our analysis can help to gain understanding on the differential 3D chromatin architecture in loci containing oncogenes and tumor suppressor genes.