The Hi-C method is widely used to study the functional roles of the three-dimensional (3D) architecture of genomes. Here, we integrate Hi-C, whole-genome sequencing (WGS) and RNA-seq to study the 3D genome architecture of multiple myeloma (MM) and how it associates with genomic variation and gene expression. Our results show that Hi-C interaction matrices are biased by copy number variations (CNVs) and can be used to detect CNVs. Also, combining Hi-C and WGS data can improve the detection of translocations. We find that CNV breakpoints significantly overlap with topologically associating domain (TAD) boundaries. Compared to normal B cells, the numbers of TADs increases by 25% in MM, the average size of TADs is smaller, and about 20% of genomic regions switch their chromatin A/B compartment types. In summary, we report a 3D genome interaction map of aneuploid MM cells and reveal the relationship among CNVs, translocations, 3D genome reorganization, and gene expression regulation.
Highlights d Low-input tagHi-C captures the chromatin structures using hundreds of cells d Compartment and the Rabl configuration are dynamic during hematopoiesis d Gene-body-associating domains (GADs) are general structures of highly expressed genes d Spatial chromatin loops link GWAS SNPs to candidate bloodphenotype genes
We develop a method called open chromatin enrichment and network Hi-C (OCEAN-C) for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C, OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. We identify more than 10,000 hubs of open chromatin interactions (HOCIs) in human cells, which are mainly active promoters and enhancers bound by many DNA-binding proteins and form interaction networks crucial for gene transcription. In addition to identifying large-scale topological structures, including topologically associated domains and A/B compartments, OCEAN-C can detect HOCI-mediated chromatin interactions that are strongly associated with gene expression, super-enhancers, and broad H3K4me3 domains.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1430-4) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.