Stratifying TAD boundaries pinpoints focal genomic regions of regulation, damage, and repair

作者：Bijia Chen, Chao Ren, Zhangyi Ouyang, Jingxuan Xu, Kang Xu, Yaru Li, Hejiang Guo, Xuemei Bai, Mengge Tian, Xiang Xu, Yuyang Wang, Hao Li, Xiaochen Bo, Hebing Chen · 发表于：Briefings in Bioinformatics · 年份：2024 · DOI：10.1093/bib/bbae306 · 被引用次数：8 · 研究领域：Genomics and Chromatin Dynamics、RNA Research and Splicing、Chromosomal and Genetic Variations

Advances in chromatin mapping have exposed the complex chromatin hierarchical organization in mammals, including topologically associating domains (TADs) and their substructures, yet the functional implications of this hierarchy in gene regulation and disease progression are not fully elucidated. Our study delves into the phenomenon of shared TAD boundaries, which are pivotal in maintaining the hierarchical chromatin structure and regulating gene activity. By integrating high-resolution Hi-C data, chromatin accessibility, and DNA double-strand breaks (DSBs) data from various cell lines, we systematically explore the complex regulatory landscape at high-level TAD boundaries. Our findings indicate that these boundaries are not only key architectural elements but also vibrant hubs, enriched with functionally crucial genes and complex transcription factor binding site-clustered regions. Moreover, they exhibit a pronounced enrichment of DSBs, suggesting a nuanced interplay between transcriptional regulation and genomic stability. Our research provides novel insights into the intricate relationship between the 3D genome structure, gene regulation, and DNA repair mechanisms, highlighting the role of shared TAD boundaries in maintaining genomic integrity and resilience against perturbations. The implications of our findings extend to understanding the complexities of genomic diseases and open new avenues for therapeutic interventions targeting the structural and functional integrity ...