한빛사논문
Jaegeon Joo1,†, Sunghyun Cho2,†, Sukbum Hong2, Sunwoo Min1, Kyukwang Kim1, Rajeev Kumar4, Jeong-Mo Choi4, Yongdae Shin2,3,* and Inkyung Jung1,*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
2Department of Mechanical Engineering, Seoul National University, Seoul 08826, Republic of Korea
3Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea
4Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea
*To whom correspondence should be addressed.
Correspondence may also be addressed to Yongdae Shin.
†The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
Abstract
Inter-chromosomal interactions play a crucial role in genome organization, yet the organizational principles remain elusive. Here, we introduce a novel computational method to systematically characterize inter-chromosomal interactions using in situ Hi-C results from various cell types. Our method successfully identifies two apparently hub-like inter-chromosomal contacts associated with nuclear speckles and nucleoli, respectively. Interestingly, we discover that nuclear speckle-associated inter-chromosomal interactions are highly cell-type invariant with a marked enrichment of cell-type common super-enhancers (CSEs). Validation using DNA Oligopaint fluorescence in situ hybridization (FISH) shows a strong but probabilistic interaction behavior between nuclear speckles and CSE-harboring genomic regions. Strikingly, we find that the likelihood of speckle-CSE associations can accurately predict two experimentally measured inter-chromosomal contacts from Hi-C and Oligopaint DNA FISH. Our probabilistic establishment model well describes the hub-like structure observed at the population level as a cumulative effect of summing individual stochastic chromatin-speckle interactions. Lastly, we observe that CSEs are highly co-occupied by MAZ binding and MAZ depletion leads to significant disorganization of speckle-associated inter-chromosomal contacts. Taken together, our results propose a simple organizational principle of inter-chromosomal interactions mediated by MAZ-occupied CSEs.
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