Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [bulk RNA-seq]

In this study, we performed network analysis on Hi-C data and identified a group of non-coding regions forming many 3D contacts (referred to as hubs). Through a high-throughput CRISPR-Cas9 library screening by targeted deletion, we discovered that some hubs without any epigenetic marks were essential for cell growth and survival. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact the distal genes expression. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of disease-associated genetic variations. Furthermore, our analyses also suggest a powerful approach to develop "one-drug-multiple-targets" therapeutics targeting disease-specific non-coding regions. Examination of the mRNA profiles of K562 cells infected with pgRNA targeting AAVS1 locus