Formation of chromosomal domains by loop extrusion. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Three-dimensional folding and functional organization principles of the Drosophila genome. Topological domains in mammalian genomes identified by analysis of chromatin interactions. CTCF-mediated human 3D genome architecture reveals chromatin topology for transcription. Looping and interaction between hypersensitive sites in the active β-globin locus. Tolhuis, B., Palstra, R.-J., Splinter, E., Grosveld, F. This review captures the recent state of the field and defines some of the basic principles that shape genome organization. The self-organizing genome: principles of genome architecture and function. However, approaches that more comprehensively integrate a wide variety of genomic and imaging datasets are still needed to uncover the functional role of 3D genome structure in defining cellular phenotypes in health and disease. Here, we discuss how recently developed computational tools, including machine-learning-based methods and integrative structure-modelling frameworks, have led to a systematic, multiscale delineation of the connections among different scales of 3D genome organization, genomic and epigenomic features, functional nuclear components and genome function. In parallel, advanced computational methods have been developed to leverage these mapping data to reveal multiscale three-dimensional (3D) genome features and to provide a more complete view of genome structure and its connections to genome functions such as transcription. Recent progress in whole-genome mapping and imaging technologies has enabled the characterization of the spatial organization and folding of the genome in the nucleus.
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