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

• Published in: Nature Communications
• Main Authors: Claudia Fierro, Veronica Gatti, Veronica La Banca, Sara De Domenico, Stefano Scalera, Giacomo Corleone, Maurizio Fanciulli, Francesca De Nicola, Alessandro Mauriello, Manuela Montanaro, George A. Calin, Gerry Melino, Angelo Peschiaroli
• Format: Article
• Language: English
• Published: Nature Portfolio 2023-06-01
• Online Access: https://doi.org/10.1038/s41467-023-39011-5

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.