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    Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription

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    Authors
    Giorgetti, Luca
    Galupa, Rafael
    Nora, Elphege P.
    Piolot, Tristan
    Lam, France
    Dekker, Job
    Tiana, Guido
    Heard, Edith
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Program in Systems Biology
    Document Type
    Journal Article
    Publication Date
    2014-05-08
    Keywords
    Biochemistry
    Molecular Biology
    Molecular Genetics
    Structural Biology
    Systems Biology
    
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    Link to Full Text
    http://dx.doi.org/10.1016/j.cell.2014.03.025
    Abstract
    A new level of chromosome organization, topologically associating domains (TADs), was recently uncovered by chromosome conformation capture (3C) techniques. To explore TAD structure and function, we developed a polymer model that can extract the full repertoire of chromatin conformations within TADs from population-based 3C data. This model predicts actual physical distances and to what extent chromosomal contacts vary between cells. It also identifies interactions within single TADs that stabilize boundaries between TADs and allows us to identify and genetically validate key structural elements within TADs. Combining the model's predictions with high-resolution DNA FISH and quantitative RNA FISH for TADs within the X-inactivation center (Xic), we dissect the relationship between transcription and spatial proximity to cis-regulatory elements. We demonstrate that contacts between potential regulatory elements occur in the context of fluctuating structures rather than stable loops and propose that such fluctuations may contribute to asymmetric expression in the Xic during X inactivation.
    Source
    Giorgetti L, Galupa R, Nora EP, Piolot T, Lam F, Dekker J, Tiana G, Heard E. Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription. Cell. 2014 May 8;157(4):950-63. doi:10.1016/j.cell.2014.03.025. Link to article on publisher's site
    DOI
    10.1016/j.cell.2014.03.025
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49926
    PubMed ID
    24813616
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cell.2014.03.025
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