Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells
- La Sapienza University of Rome, Italy
- La Sapienza University of Rome, National Research Council (CNR), Italy
- Sapienza University of Rome, Italy
- Istituto Italiano di Tecnologia, Italy
- La Sapienza, University of Rome, Italy
- National Research Council (CNR) at Sapienza University of Rome, Italy
Abstract
Skeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cells (MuSCs) activity. This ability requires the proper balance between MuSCs expansion and differentiation which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated lncRNA, Lnc-Rewind, which is expressed in murine MuSCs and conserved in human. We find that, in mouse, Lnc-Rewind acts as an epigenetic regulator of MuSCs proliferation and expansion by influencing the expression of skeletal muscle genes and several components of the WNT (Wingless-INT) signalling pathway. Among them, we identified the nearby Wnt7b gene as a direct Lnc-Rewind target. We show that Lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates the in cis repression of Wnt7b by H3K9me2 deposition. Overall, these findings provide novel insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.
Data availability
Sequencing data have been deposited in GEO under accession code GSE141396. All data generated or analysed during this study are included in the manuscript and supporting files
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Discovery of Novel LncRNA species differentially expressed during murine muscle differentiationEuropean Nucleotide Archive (ENA) accession number, PRJEB6112.
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Gene expression profiling of human and murine in vitro muscle differentiationGene Expression Omnibus (GEO) accession number, GSE70389.
Article and author information
Author details
Funding
Sapienza Università di Roma (prot. RM11715C7C8176C1)
- Monica Ballarino
Sapienza Università di Roma (RM11916B7A39DCE5)
- Monica Ballarino
Ministero dell'Istruzione, dell'Università e della Ricerca (RBSI14QMG0)
- Chiara Mozzetta
Associazione Italiana per la Ricerca sul Cancro (MyFIRST grant n.18993)
- Chiara Mozzetta
AFM-Telethon (#22489)
- Chiara Mozzetta
Collection of National Chemical Compounds and Screening Center (LIFE2020-Regione Lazio)
- Chiara Mozzetta
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: For the experiments described in this study, C57/BL10 wild-type mice were used and differences which were observed in both male and female mice were included in experiments. Animals were treated in respect to housing, nutrition and care according to the guidelines of Good laboratory Practice (GLP). All experimental protocols (Protocol N{degree sign} 7FF2C.4 -Authorization N{degree sign} 746/2016-PR) were approved and conformed to the regulatory standards. All animals were kept in a temperature of 22{degree sign}C {plus minus} 3{degree sign}C with a humidity between 50% and 60%, in animal cages with at least 5 animals.
Copyright
© 2021, Cipriano et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells
eLife 10:e54782.
https://doi.org/10.7554/eLife.54782
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