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

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 betwe...

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Autores principales: Fierro, Claudia, Gatti, Veronica, La Banca, Veronica, De Domenico, Sara, Scalera, Stefano, Corleone, Giacomo, Fanciulli, Maurizio, De Nicola, Francesca, Mauriello, Alessandro, Montanaro, Manuela, Calin, George A., Melino, Gerry, Peschiaroli, Angelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293300/
https://www.ncbi.nlm.nih.gov/pubmed/37365156
http://dx.doi.org/10.1038/s41467-023-39011-5
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author Fierro, Claudia
Gatti, Veronica
La Banca, Veronica
De Domenico, Sara
Scalera, Stefano
Corleone, Giacomo
Fanciulli, Maurizio
De Nicola, Francesca
Mauriello, Alessandro
Montanaro, Manuela
Calin, George A.
Melino, Gerry
Peschiaroli, Angelo
author_facet Fierro, Claudia
Gatti, Veronica
La Banca, Veronica
De Domenico, Sara
Scalera, Stefano
Corleone, Giacomo
Fanciulli, Maurizio
De Nicola, Francesca
Mauriello, Alessandro
Montanaro, Manuela
Calin, George A.
Melino, Gerry
Peschiaroli, Angelo
author_sort Fierro, Claudia
collection PubMed
description 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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spelling pubmed-102933002023-06-28 The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation Fierro, Claudia Gatti, Veronica La Banca, Veronica De Domenico, Sara Scalera, Stefano Corleone, Giacomo Fanciulli, Maurizio De Nicola, Francesca Mauriello, Alessandro Montanaro, Manuela Calin, George A. Melino, Gerry Peschiaroli, Angelo Nat Commun Article 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. Nature Publishing Group UK 2023-06-26 /pmc/articles/PMC10293300/ /pubmed/37365156 http://dx.doi.org/10.1038/s41467-023-39011-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fierro, Claudia
Gatti, Veronica
La Banca, Veronica
De Domenico, Sara
Scalera, Stefano
Corleone, Giacomo
Fanciulli, Maurizio
De Nicola, Francesca
Mauriello, Alessandro
Montanaro, Manuela
Calin, George A.
Melino, Gerry
Peschiaroli, Angelo
The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
title The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
title_full The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
title_fullStr The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
title_full_unstemmed The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
title_short The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
title_sort long non-coding rna neat1 is a δnp63 target gene modulating epidermal differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293300/
https://www.ncbi.nlm.nih.gov/pubmed/37365156
http://dx.doi.org/10.1038/s41467-023-39011-5
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