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    Remodeling of Three-Dimensional Organization of the Nucleus during Terminal Keratinocyte Differentiation in the Epidermis

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    Publication date
    2013
    Author
    Gdula, Michal R.
    Poterlowicz, Krzysztof
    Mardaryev, Andrei N.
    Sharov, A.A.
    Fessing, Michael Y.
    Botchkarev, Vladimir A.
    Peng, Yonghong
    Keyword
    Keratinocytes; Differentiation; Epidermis; Nucleus; Genome organization; Human skin; Pathology; REF 2014
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    The nucleus of epidermal keratinocytes (KCs) is a complex and highly compartmentalized organelle, whose structure is markedly changed during terminal differentiation and transition of the genome from a transcriptionally active state seen in the basal and spinous epidermal cells to a fully inactive state in the keratinized cells of the cornified layer. Here, using multicolor confocal microscopy, followed by computational image analysis and mathematical modeling, we demonstrate that in normal mouse footpad epidermis, transition of KCs from basal epidermal layer to the granular layer is accompanied by marked differences in nuclear architecture and microenvironment including the following: (i) decrease in the nuclear volume; (ii) decrease in expression of the markers of transcriptionally active chromatin; (iii) internalization and decrease in the number of nucleoli; (iv) increase in the number of pericentromeric heterochromatic clusters; and (v) increase in the frequency of associations between the pericentromeric clusters, chromosomal territory 3, and nucleoli. These data suggest a role for nucleoli and pericentromeric heterochromatin clusters as organizers of nuclear microenvironment required for proper execution of gene expression programs in differentiating KCs, and provide important background information for further analyses of alterations in the topological genome organization seen in pathological skin conditions, including disorders of epidermal differentiation and epidermal tumors.
    URI
    http://hdl.handle.net/10454/7221
    Version
    No full-text in the repository
    Citation
    Gdula MR, Poterlowicz K, Mardaryev AN et al (2013) Remodeling of Three-Dimensional Organization of the Nucleus during Terminal Keratinocyte Differentiation in the Epidermis. Journal of Investigative Dermatology. 133(9): 2191-2201.
    Link to publisher’s version
    http://dx.doi.org/10.1038/jid.2013.66
    Type
    Article
    Collections
    Life Sciences Publications

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