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

Author

Listed:
  • Claudia Fierro

    (University of Rome “Tor Vergata”
    Bambino Gesù Children’s Hospital, IRCSS)

  • 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
    The University of Texas MD Anderson Cancer Center)

  • Gerry Melino

    (University of Rome “Tor Vergata”)

  • Angelo Peschiaroli

    (Institute of Translational Pharmacology (IFT), CNR)

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.

Suggested Citation

  • Claudia Fierro & Veronica Gatti & Veronica Banca & Sara Domenico & Stefano Scalera & Giacomo Corleone & Maurizio Fanciulli & Francesca Nicola & Alessandro Mauriello & Manuela Montanaro & George A. Cal, 2023. "The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39011-5
    DOI: 10.1038/s41467-023-39011-5
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    References listed on IDEAS

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    1. Dimple Chakravarty & Andrea Sboner & Sujit S. Nair & Eugenia Giannopoulou & Ruohan Li & Sven Hennig & Juan Miguel Mosquera & Jonathan Pauwels & Kyung Park & Myriam Kossai & Theresa Y. MacDonald & Jacq, 2014. "The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer," Nature Communications, Nature, vol. 5(1), pages 1-16, December.
    2. Fulai Jin & Yan Li & Jesse R. Dixon & Siddarth Selvaraj & Zhen Ye & Ah Young Lee & Chia-An Yen & Anthony D. Schmitt & Celso A. Espinoza & Bing Ren, 2013. "A high-resolution map of the three-dimensional chromatin interactome in human cells," Nature, Nature, vol. 503(7475), pages 290-294, November.
    3. Annie Yang & Ronen Schweitzer & Deqin Sun & Mourad Kaghad & Nancy Walker & Roderick T. Bronson & Cliff Tabin & Arlene Sharpe & Daniel Caput & Christopher Crum & Frank McKeon, 1999. "p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development," Nature, Nature, vol. 398(6729), pages 714-718, April.
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