We summarize the current knowledge of organization and functional impact of 3D chromatin structure.
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TADs help biological interpretation but are hard to define due to fractal properties of chromatin.
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Disrupting chromatin topology can lead to drastic phenotypes emphasizing its functional importance.
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We propose two models how 3D chromatin contacts affect distal sites: ‘Spreading’ vs ‘Touch and Act’.
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Combining HiC-type data with microscopy and CRISPR promises functional insights of 3D contacts.
Abstract
Understanding how the genome is compacted in a highly ordered structure that fits in the eukaryotic nucleus, while keeping its capacity of orchestrating the functionality of the cell, is one of the long-standing questions in biology. While the recent technological advances in chromosome conformation capture experiments have provided extensive knowledge about the structural organisation of chromatin, our understanding of the functional impact of these arrangements on downstream processes, and how structure translates into function, is just beginning to emerge. In this review we summarize our current knowledge of the three-dimensional chromatin organisation, the mechanisms of how it is established and maintained, and the functional impact it has on gene regulation and complex phenotypes. We will end with a discussion on the future developments of this fast-paced field.