Journal
SCIENCE ADVANCES
Volume 7, Issue 45, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abi6020
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Funding
- CIRM [RB5-07012]
- NIH [R01HG009626]
- National Science Foundation of China [NSFC31930016]
- Beijing Municipal Science and Technology Commission [Z181100001318009]
- Beijing Advanced Innovation Center for Genomics at Peking University
- Peking-Tsinghua Center for Life Sciences
- China Postdoctoral Science Foundation [2020 M670031]
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This study revealed the structural importance of noncoding loci that are not associated with any functional element, providing a previously unknown mechanistic understanding of disease-associated genetic variations (GVs). Additionally, it suggests a potential approach for developing therapeutics targeting disease-specific noncoding regions essential for disease cell survival.
Most noncoding regions of the human genome do not harbor any annotated element and are even not marked with any epigenomic or protein binding signal. However, an overlooked aspect of their possible role in stabilizing 3D chromatin organization has not been extensively studied. To illuminate their structural importance, we started with the noncoding regions forming many 3D contacts (referred to as hubs) and performed a CRISPR library screening to identify dozens of hubs essential for cell viability. Hi-C and single-cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and affect the expressions of distal genes. This study revealed the 3D structural importance of noncoding loci that are not associated with any functional element, providing a previously unknown mechanistic understanding of disease-associated genetic variations (GVs). Furthermore, our analyses also suggest a possible approach to develop therapeutics targeting disease-specific noncoding regions that are critical for disease cell survival.
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