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

Mardaryev, A.N.; Liu, B.; Rapisarda, V.; Poterlowicz, K.; Malashchuk, I.; Rudolf, J.; Sharov, A.A.; Jahoda, C.A.; Fessing, M.Y.; Benitah, S.A.; Xu, G.-L.; Botchkarev, V.A.

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


Authors

A.N. Mardaryev

B. Liu

V. Rapisarda

K. Poterlowicz

I. Malashchuk

J. Rudolf

A.A. Sharov

M.Y. Fessing

S.A. Benitah

G.-L. Xu

V.A. Botchkarev



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.

Citation

Mardaryev, A., Liu, B., Rapisarda, V., Poterlowicz, K., Malashchuk, I., Rudolf, J., …Botchkarev, V. (2016). Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium. Journal of Cell Biology, 212(1), 77-89. https://doi.org/10.1083/jcb.201506065

Journal Article Type Article
Acceptance Date Nov 17, 2015
Online Publication Date Dec 28, 2015
Publication Date Jan 4, 2016
Deposit Date Sep 20, 2016
Publicly Available Date Sep 20, 2016
Journal Journal of Cell Biology
Print ISSN 0021-9525
Electronic ISSN 1540-8140
Publisher Rockefeller University Press
Peer Reviewed Peer Reviewed
Volume 212
Issue 1
Pages 77-89
DOI https://doi.org/10.1083/jcb.201506065

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http://creativecommons.org/licenses/by-nc-sa/3.0

Copyright Statement
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).





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