TY - JOUR
T1 - The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
AU - Fierro, Claudia
AU - Gatti, Veronica
AU - La Banca, Veronica
AU - De Domenico, Sara
AU - Scalera, Stefano
AU - Corleone, Giacomo
AU - Fanciulli, Maurizio
AU - De Nicola, Francesca
AU - Mauriello, Alessandro
AU - Montanaro, Manuela
AU - Calin, George A.
AU - Melino, Gerry
AU - Peschiaroli, Angelo
N1 - Funding Information:
The authors thank Prof. Francesca Bernassola for critical suggestions. This work has been supported by the Associazione Italiana per la Ricerca contro il Cancro (AIRC) to A.P. (IG#24678), PRIN2017XCXAFZ to A.P. This work has been also partially supported by the Lazio Innova Progetto Gruppo di Ricerca 2020 A0375-2020-36585 to A.P.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-39011-5
DO - 10.1038/s41467-023-39011-5
M3 - Article
C2 - 37365156
AN - SCOPUS:85163414192
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3795
ER -