PMID- 37013988 OWN - NLM STAT- MEDLINE DCOM- 20230626 LR - 20231116 IS - 1362-4962 (Electronic) IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 51 IP - 11 DP - 2023 Jun 23 TI - Probabilistic establishment of speckle-associated inter-chromosomal interactions. PG - 5377-5395 LID - 10.1093/nar/gkad211 [doi] AB - 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. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. FAU - Joo, Jaegeon AU - Joo J AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. FAU - Cho, Sunghyun AU - Cho S AD - Department of Mechanical Engineering, Seoul National University, Seoul 08826, Republic of Korea. FAU - Hong, Sukbum AU - Hong S AD - Department of Mechanical Engineering, Seoul National University, Seoul 08826, Republic of Korea. FAU - Min, Sunwoo AU - Min S AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. FAU - Kim, Kyukwang AU - Kim K AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. FAU - Kumar, Rajeev AU - Kumar R AD - Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea. FAU - Choi, Jeong-Mo AU - Choi JM AUID- ORCID: 0000-0003-2656-4851 AD - Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea. FAU - Shin, Yongdae AU - Shin Y AUID- ORCID: 0000-0003-3441-1986 AD - Department of Mechanical Engineering, Seoul National University, Seoul 08826, Republic of Korea. AD - Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea. FAU - Jung, Inkyung AU - Jung I AUID- ORCID: 0000-0002-5885-2754 AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (Chromatin) RN - 9007-49-2 (DNA) SB - IM MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Chromosomes MH - *Chromatin/genetics/metabolism MH - Cell Nucleus/metabolism MH - DNA/genetics/metabolism PMC - PMC10287923 EDAT- 2023/04/05 06:00 MHDA- 2023/06/26 06:42 PMCR- 2023/04/04 CRDT- 2023/04/04 07:22 PHST- 2023/03/25 00:00 [accepted] PHST- 2023/03/08 00:00 [revised] PHST- 2022/06/19 00:00 [received] PHST- 2023/06/26 06:42 [medline] PHST- 2023/04/05 06:00 [pubmed] PHST- 2023/04/04 07:22 [entrez] PHST- 2023/04/04 00:00 [pmc-release] AID - 7103213 [pii] AID - gkad211 [pii] AID - 10.1093/nar/gkad211 [doi] PST - ppublish SO - Nucleic Acids Res. 2023 Jun 23;51(11):5377-5395. doi: 10.1093/nar/gkad211.