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22.7: Mechanistic Understanding of Genome Architecture

  • Page ID
    41056
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    Organization of chromosomes, particularly in spatial relation to other parts of the chromosome, is not well understood during the mitotic process. The conformation of cells is thought to conform to two di↵erent states. Highly compartmentalized and cell-type specific conformations are almost entirely limited to interphase. During the transition into metaphase, chromosomes enter a locus and tissue-independent folding state.

    During the mitotic process, approximately 30% of LADs are positioned along the cellular periphery. This positioning, however, reflects protein-lamina contact at intermittent intervals, however, the cells are restricted to the periphery of the cells. During mitotic division, this laminar positioning is stochastically inherited by child cells.


    pro-metaphase.jpg
    Figure 22.14: LADs Through The (Single) Cell Cycle (Kind et al, Cell 2013)

    Courtesy of Elsevier, Incorporate, Used with permission.

    Source: Kind, Jop, et al. "Single-cell Dynamics of Genome nuclear

    Lamina Interactions." Cell 153, no. 1 (2013): 178-92

    Modeling

    Three dimensional modeling will be increasingly important in understanding the chromosomal interactions. Current techniques have modeled the yeast genome and the ↵ -globin locus (Duan et al. Nature (2010), Bau et al. Nature SMB (2011)). From modeling studeis it has become clear that we cannot generate a direct relationship between contact probability and spatial distance (i.e. contact probability != spatial distance).

    Modelling, however, is an inverse problem, it is harder to go one way than the other. Specifically, it is easier to go from protein structure to a protein contact map than vice versa. Similarly, chromosomal structure is a hard problem, even if we have a contact mapping.

    Interphase.jpg
    Figure 22.15: Loop Extrusion as a Mechanism of Chromosome Orientation

    This page titled 22.7: Mechanistic Understanding of Genome Architecture is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Manolis Kellis et al. (MIT OpenCourseWare) via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is available upon request.