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Chunk #8 — Chromosome folding

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Epigenomics and the structure of the living genome.
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Several key insights into chromosome folding have been afforded by 3C-based methods. In many organisms, Hi-C reveals robust interactions between centromeres of different chromosomes, and similarly between various telomeres, consistent with the long-understood Rabl configuration of chromosomes in which centromeres cluster at the nuclear periphery due to their association with the spindle pole body (SPB), with chromosomes extending from the SPB to a point of telomeric attachment to the nuclear periphery (Duan et al. 2010; Feng et al. 2014; Marbouty et al. 2014). Beyond this genomic confirmation of the Rabl configuration, at relatively low resolution, Hi-C generally reveals two major compartments of active and repressed chromatin, with megabase-scale blocks of chromatin that preferentially interact with other blocks of the same type (Lieberman-Aiden et al. 2009; Feng et al. 2014). More recently, higher resolution Hi-C studies in many organisms reveal a common folding motif variously referred to as topologically associating domains (TADs), or chromosomally interacting domains (CIDs) (Dixon et al. 2012; Nora et al. 2012; Sexton et al. 2012; Le et al. 2013; Mizuguchi et al. 2014; Hsieh et al. 2015;