title: Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium.
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.
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Yorkshire BD7 1DP, England, UK.
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Mardaryev
authors.affiliation: The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Yorkshire BD7 1DP, England, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rapisarda
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Yorkshire BD7 1DP, England, UK.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Poterlowicz
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Yorkshire BD7 1DP, England, UK.
authors.forename: Igor
authors.initials: I
authors.lastname: Malashchuk
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Yorkshire BD7 1DP, England, UK.
authors.forename: Jana
authors.initials: J
authors.lastname: Rudolf
authors.affiliation: Department of Dermatology, Boston University School of Medicine, Boston, MA 02118.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Sharov
authors.affiliation: School of Biological Sciences, University of Durham, Durham DH1 3LE, England, UK.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Jahoda
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Yorkshire BD7 1DP, England, UK.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Fessing
authors.affiliation: Institute for Research in Biomedicine, 08028 Barcelona, Spain Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Spain.
authors.forename: Salvador A
authors.initials: SA
authors.lastname: Benitah
authors.affiliation: The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xu
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Yorkshire BD7 1DP, England, UK Department of Dermatology, Boston University School of Medicine, Boston, MA 02118 v.a.botchkarev@bradford.ac.uk vladbotc@bu.edu.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Botchkarev
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism*; D008025:Ligases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063150:Polycomb Repressive Complex 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D063150:Polycomb Repressive Complex 1; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570504:Cbx4 protein, mouse