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.

doi:10.1083/jcb.201506065

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.

Authors

A.N. Mardaryev

B. Liu

V. Rapisarda

K. Poterlowicz

I. Malashchuk

J. Rudolf

A.A. Sharov

Professor Colin Jahoda colin.jahoda@durham.ac.uk
Professor

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
Public URL	https://durham-repository.worktribe.com/output/1374672

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