期刊
GENOME BIOLOGY
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13059-019-1904-z
关键词
Chromatin folding; Polymer modeling; Super-enhancers; Topologically associated domains; Epigenomics; Histone modifications; Sequential Monte Carlo sampling; Gibbs sampling; Bayesian inference; Machine learning; CHROMATIX
资金
- NIH [R21AI126308, R21AI137865, R01CA204962, R35GM127084]
- [CAS-18H100000104]
- [NSFC-81627801]
Chromatin interactions are important for gene regulation and cellular specialization. Emerging evidence suggests many-body spatial interactions play important roles in condensing super-enhancer regions into a cohesive transcriptional apparatus. Chromosome conformation studies using Hi-C are limited to pairwise, population-averaged interactions; therefore unsuitable for direct assessment of many-body interactions. We describe a computational model, CHROMATIX, which reconstructs ensembles of single-cell chromatin structures by deconvolving Hi-C data and identifies significant many-body interactions. For a diverse set of highly active transcriptional loci with at least 2 super-enhancers, we detail the many-body functional landscape and show DNase accessibility, POLR2A binding, and decreased H3K27me3 are predictive of interaction-enriched regions.
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