Organization of the mitotic chromosome

By N. Naumova, Maxim Imakaev, Geoffrey Fudenberg, Y. Zhan, B. Lajoie, Leonid A. Mirny, Job Dekker. Science, 2013

943 citations recorded by the source corpus.

Chromosome Conundrum The three-dimensional organization of chromosomal DNA within the cell nucleus plays an important role in gene regulation. Naumova et al. (p. 948, published online 7 November; see the Perspective by Kleckner et al.) used chromosome conformation capture-based methods in human tissue culture cells to analyze the higher order folding of human chromosomes across the cell cycle. During interphase the chromosomes showed locus-specific compart-mentalization. In mitotic cells, on the other hand, the chromosome organization was more linear, consistent with arrays of consecutive chromatin loops. Chromosome conformation changes dramatically during the cell cycle and is unlikely to carry epigenetic information. [Also see Perspective by Kleckner et al.] Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type–specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ed31b9adb1c3acb1a8f4b92b5ae58abceb56f1d2

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Citations in the corpus

A pathway for mitotic chromosome formation (2018, background): “Hi-C analysis revealed that in the absence of SMC2, interphase compartments and TADs were still present and largely unaffected by late prophase, at a time when they were completely dis- assembled in the wild type (t = 10 min) (Fig.”
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes (2014, positive): “…of mammalian chromosome structure have suggested that they are organized into a hierarchy of units, which include Topologically Associating Domains (TADs) and gene loops (Figure 1A)(Dixon et al., 2012; Filippova et al., 2014; Gibcus and Dekker, 2013; Naumova et al., 2013; Nora et al., 2012).”
Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II, and Pol III (2020, background): “Previous studies have reported that TAD structures disappear in mitosis and reestablish in the early G1 phase[47].”
Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells (2018, background): “Because cells undergo major chromatin reorganization during mitosis (39), these TAD-like structures were likely reestablished after mitosis.”
Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition (2017, background): “Simulations of decondensation subject to loop extrusion that start from a metaphase chromosome 11 (Fig.”
Formation of Chromosomal Domains by Loop Extrusion (2015, methodology): “As described previously (Naumova et al., 2013), we modeled”
Cell-cycle dynamics of chromosomal organisation at single-cell resolution (2016, positive): “Consistent with previous reports at lower temporal resolution 11 , we show chromosome condensation in preparation for mitosis, and rapid expansion in early G1, while also finding extensive remodelling during replication.”
Ever-changing landscapes: transcriptional enhancers in development and evolution (2016, background): “Notably, the invariance of TADs across cell states is not due to a passive maintenance from one cell division to the next, as TAD structures are lost during mitosis to accommodate an alternative conformational state of metaphase chromosomes (Naumova et al., 2013) (Figure 3E).”