Radiation-induced Hierarchical Topologically Associated Domain Change and Its Role in Cellular Responses to Radiation / 中国生物化学与分子生物学报

ABSTRACT

The three-dimensional (3D) genome organization plays an important role in gene regulation. As a basic functional unit of the genome, topologically associated domain (TAD) regulates multiplebiological processes such as gene expression and DNA replication and plays a role in radiation-inducedDNA damage repair. Recent studies showed that TAD is not a completely independent domain butcontains hierarchical internal domains, which could be a new mechanism of gene regulation. To explorethe role of hierarchical TAD in cellular responses to radiation, we apply the OnTAD algorithm, anoptimized nested TAD caller from Hi-C data, to identify hierarchical TAD in 26 Hi-C data from Geneexpression omnibus (GEO) database. These data were from irradiated fibroblasts, lymphoblasts andfibroblasts deficient in the ataxia telangiectasia mutated (ATM) gene with 5 Gy X-ray. We observe thatX-ray can regularly affect the hierarchy of TAD in which high-level TAD is prone to change and low-levelTAD is more conservative. We propose that radiation-induced TAD hierarchy change can regulate cellularresponses to radiation by regulating gene expression, and ATM is a necessary factor for radiation-inducedTAD hierarchy change and recovery. This study provides new insights into the role of the 3D genome inradiation-induced cellular responses from the perspective of hierarchical TAD structures.