Epigenetic priming of an epithelial enhancer by p63 and CTCF controls expression of a skin-restricted gene XP33

The transcription factor p63 is a renowned master regulator of gene expression of stratified epithelia. While multiple proteins have been identified as p63 bona fide targets, little is known about non-coding RNAs (ncRNAs) whose transcription is controlled by p63. Here, we describe a skin-specific no...

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Bibliographic Details
Published in:Cell death discovery 2023-12, Vol.9 (1), p.446-9, Article 446
Main Authors: Smirnov, Artem, Lena, Anna Maria, Tosetti, Giulia, Yang, Xue, Cappello, Angela, Helmer Citterich, Manuela, Melino, Gerry, Candi, Eleonora
Format: Article
Language:English
Subjects:
631/337/100/102
631/337/572/2102
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Cycle Analysis
Cell death
Chromatin
Epigenetics
Gene expression
Keratinocytes
Life Sciences
Non-coding RNA
Proteins
Skin
Stem Cells
Transcription factors
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Summary:The transcription factor p63 is a renowned master regulator of gene expression of stratified epithelia. While multiple proteins have been identified as p63 bona fide targets, little is known about non-coding RNAs (ncRNAs) whose transcription is controlled by p63. Here, we describe a skin-specific non-coding RNA XP33 as a novel target of p63. XP33 levels are increased during keratinocyte differentiation in vitro, while its depletion results in decreased expression of late cornified gene LCE2D . By using publicly available multi-omics data, we show that CTCF and p63 establish an epithelial enhancer to prime XP33 transcription in a tissue-restricted manner. XP33 promoter and enhancer form a chromatin loop exclusively in keratinocytes but not in other cell types. Moreover, the XP33 enhancer is occupied by differentiation-specific factors that control XP33 transcription. Altogether, we identify a tissue-specific non-coding RNA whose expression is epigenetically regulated by p63 and CTCF.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-023-01716-3