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    Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium

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    Publication date
    2016-01-01
    Author
    Mardaryev, Andrei N.
    Liu, B.
    Rapisarda, Valentina
    Poterlowicz, Krzysztof
    Malashchuk, Igor
    Rudolf, Jana
    Sharov, A.A.
    Jahoda, C.J.
    Fessing, Michael Y.
    Benitah, S.
    Xu, G.
    Botchkarev, Vladimir A.
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    Keyword
    Skin; Development; Epidermis; Epigenetic
    Rights
    © 2016 Mardaryev et al. This article is distributed under the terms of a Creative Commons Attribution–Noncommercial–Share Alike 3.0 Unported license.
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    During development, multipotent progenitor cells establish lineage-specific programmers of gene activation and silencing underlying their differentiation into specialized cell types. We show that the Polycomb component Cbx4 serves as a critical determinant that maintains the epithelial identity in the developing epidermis by repressing nonepidermal gene expression programs. Cbx4 ablation in mice results in a marked decrease of the epidermal thickness and keratinocyte (KC) proliferation associated with activation of numerous neuronal genes and genes encoding cyclin-dependent kinase inhibitors (p16/p19 and p57). Furthermore, the chromodomain- and SUMO E3 ligase-dependent Cbx4 activities differentially regulate proliferation, differentiation, and expression of nonepidermal genes in KCs. Finally, Cbx4 expression in KCs is directly regulated by p63 transcription factor, whereas Cbx4 overexpression is capable of partially rescuing the effects of p63 ablation on epidermal development. These data demonstrate that Cbx4 plays a crucial role in the p63-regulated program of epidermal differentiation, maintaining the epithelial identity and proliferative activity in KCs via repression of the selected nonepidermal lineage and cell cycle inhibitor genes.
    URI
    http://hdl.handle.net/10454/10161
    Version
    Published version
    Citation
    Mardaryev AN, Liu B, Rapisarda V et al (2016) Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium. Journal of Cell Biology. 212(1): 77-89.
    Link to publisher’s version
    http://dx.doi.org/10.1083/jcb.201506065
    Type
    Article
    Collections
    Life Sciences Publications

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