The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation

Claudia Fierro, Veronica Gatti, Veronica Banca, Sara Domenico, Stefano Scalera, Giacomo Corleone, Maurizio Fanciulli, Francesca Nicola, Alessandro Mauriello, Manuela Montanaro, George A. Calin, Gerry Melino and Angelo Peschiaroli ()
Additional contact information
Claudia Fierro: University of Rome “Tor Vergata”
Veronica Gatti: Institute of Translational Pharmacology (IFT), CNR
Veronica Banca: University of Rome “Tor Vergata”
Sara Domenico: University of Rome “Tor Vergata”
Stefano Scalera: Advanced Diagnostics, and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute
Giacomo Corleone: Advanced Diagnostics, and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute
Maurizio Fanciulli: Advanced Diagnostics, and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute
Francesca Nicola: Advanced Diagnostics, and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute
Alessandro Mauriello: University of Rome “Tor Vergata”
Manuela Montanaro: University of Rome “Tor Vergata”
George A. Calin: The University of Texas MD Anderson Cancer Center
Gerry Melino: University of Rome “Tor Vergata”
Angelo Peschiaroli: Institute of Translational Pharmacology (IFT), CNR

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract The transcription factor ΔNp63 regulates epithelial stem cell function and maintains the integrity of stratified epithelial tissues by acting as transcriptional repressor or activator towards a distinct subset of protein-coding genes and microRNAs. However, our knowledge of the functional link between ∆Np63 transcriptional activity and long non-coding RNAs (lncRNAs) expression is quite limited. Here, we show that in proliferating human keratinocytes ∆Np63 represses the expression of the lncRNA NEAT1 by recruiting the histone deacetylase HDAC1 to the proximal promoter of NEAT1 genomic locus. Upon induction of differentiation, ∆Np63 down-regulation is associated by a marked increase of NEAT1 RNA levels, resulting in an increased assembly of paraspeckles foci both in vitro and in human skin tissues. RNA-seq analysis associated with global DNA binding profile (ChIRP-seq) revealed that NEAT1 associates with the promoter of key epithelial transcription factors sustaining their expression during epidermal differentiation. These molecular events might explain the inability of NEAT1-depleted keratinocytes to undergo the proper formation of epidermal layers. Collectively, these data uncover the lncRNA NEAT1 as an additional player of the intricate network orchestrating epidermal morphogenesis.

Date: 2023
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DOI: 10.1038/s41467-023-39011-5

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