Population-based 3D genome structure analysis reveals driving forces in spatial genome organization
[1];
- Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089,
- Department of Anatomy, University of California, San Francisco, CA 94148,, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94702,, National Center for X-Ray Tomography, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94702,
- Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089,, Department of Chemistry and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089
Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Here, our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Arnold and Mabel Beckman Foundation
- Grant/Contract Number:
- AC02-05CH11231; P41GM103445; U01HL108634; R01GM096089; 5R01 AI113009; U54DK107981-01
- OSTI ID:
- 1240760
- Alternate ID(s):
- OSTI ID: 1379243
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 113 Journal Issue: 12; ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of SciencesCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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