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p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes

Rapisarda, Valentina; Malashchuk, Igor; Asamaowei, Inemo E.; Poterlowicz, Krzysztof; Fessing, Michael Y.; Sharov, Andrey A.; Karakesisoglou, Iakowos; Botchkarev, Vladimir A.; Mardaryev, Andrei

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Authors

Valentina Rapisarda

Igor Malashchuk

Inemo E. Asamaowei

Krzysztof Poterlowicz

Michael Y. Fessing

Andrey A. Sharov

Vladimir A. Botchkarev

Andrei Mardaryev



Abstract

The maintenance of a proper nuclear architecture and 3D organization of the genes, enhancer elements and transcription machinery plays an essential role in tissue development and regeneration. Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by marked decrease in expression of several nuclear envelop-associated components (Lamin B1, Lamin A/C, SUN1, Nesprin-3, Plectin) compared to controls. Furthermore, ChIP-qPCR assay showed enrichment of p63 on Sun1, Syne3 and Plec promoters, suggesting them as p63 targets. Alterations in the nuclei shape and expression of nuclear envelope-associated proteins were accompanied by altered distribution patterns of the repressive histone marks H3K27me3, H3K9me3 and heterochromatin protein 1- alpha in p63-null keratinocytes. These changes were also accompanied by downregulation of the transcriptional activity and relocation of the keratinocyte-specific gene loci away from the sites of active transcription towards the heterochromatin-enriched repressive nuclear compartments in p63-null cells. These data demonstrate functional links between the nuclear envelope organization, chromatin architecture and gene expression in keratinocytes and suggest nuclear envelope-associated genes as important targets mediating p63-regulated gene expression programme in the epidermis.

Citation

Rapisarda, V., Malashchuk, I., Asamaowei, I. E., Poterlowicz, K., Fessing, M. Y., Sharov, A. A., …Mardaryev, A. (2017). p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes. Journal of Investigative Dermatology, 137(10), 2157-2167. https://doi.org/10.1016/j.jid.2017.05.013

Journal Article Type Article
Acceptance Date May 1, 2017
Online Publication Date Jun 6, 2017
Publication Date Jun 6, 2017
Deposit Date Sep 1, 2017
Publicly Available Date Sep 1, 2017
Journal Journal of Investigative Dermatology
Print ISSN 0022-202X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 137
Issue 10
Pages 2157-2167
DOI https://doi.org/10.1016/j.jid.2017.05.013

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