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

Rapisarda, Valentina and Malashchuk, Igor and Asamaowei, Inemo E. and Poterlowicz, Krzysztof and Fessing, Michael Y. and Sharov, Andrey A. and Karakesisoglou, Iakowos and Botchkarev, Vladimir A. and Mardaryev, Andrei (2017) 'p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes.', Journal of investigative dermatology., 137 (10). pp. 2157-2167.


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.

Item Type:Article
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Publisher statement:This article is available under the terms of the Creative Commons Attribution License (CC BY). You may copy and distribute the article, create extracts, abstracts and new works from the article, alter and revise the article, text or data mine the article and otherwise reuse the article commercially (including reuse and/or resale of the article) without permission from Elsevier. You must give appropriate credit to the original work, together with a link to the formal publication through the relevant DOI and a link to the Creative Commons user license above. You must indicate if any changes are made but not in any way that suggests the licensor endorses you or your use of the work.
Date accepted:01 May 2017
Date deposited:01 September 2017
Date of first online publication:06 June 2017
Date first made open access:21 September 2017

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