Journal Article

The three-dimensional genome organization of Drosophila melanogaster through data integration

Chiolo, Irene, Gong, Ke, Tjong, Harianto, Li, Qingjiao, Li, Xiao, Alber, Frank, Zhou, Xianghong Jasmine

2017

Overview

Background Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome’s organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Results Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Conclusions Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: 3D genome structure / Animal Genetics and Genomics / Animals / Bioinformatics / Biomedical and Life Sciences / case studies / Cell Nucleus - chemistry / Cell Nucleus - ultrastructure / Chromosomal Proteins, Non-Histone - genetics / Chromosomal Proteins, Non-Histone - metabolism / Chromosome Mapping - methods / Chromosomes / Chromosomes, Insect - chemistry / Chromosomes, Insect - ultrastructure / Conformation / data collection / Data integration / Data Mining - statistics & numerical data / Drosophila melanogaster / Drosophila melanogaster - genetics / Drosophila melanogaster - growth & development / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Embryo, Nonmammalian / eukaryotic cells / Evolutionary Biology / Experiments / Functional morphology / Gene expression / Gene Expression Regulation, Developmental / Generalized linear models / Genetic Heterogeneity / genome / Genome, Insect / Genomes / heterochromatin / Heterochromatin - chemistry / Heterochromatin - ultrastructure / Hi-C / Higher order genome organization / Human Genetics / image analysis / In Situ Hybridization, Fluorescence / Insects / Integration / Lamina-DamID / Life Sciences / Maximum entropy method / Microbial Genetics and Genomics / Multigene Family / Nuclear Proteins - genetics / Nuclear Proteins - metabolism / Plant Genetics and Genomics / Population / Population-based modeling / topology / Transcription Factors - genetics / Transcription Factors - metabolism / Transcription, Genetic