Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells

Abstract
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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

The following previously published data sets were used

1. Ballarino M
2. Cazzella V
3. D'Andrea D
4. Grassi L
5. Bisceglie L
6. Cipriano A
7. Santini T
8. Pinnarò C
9. Morlando M
10. Tramontano A
11. Bozzoni I
(2014) Discovery of Novel LncRNA species differentially expressed during murine muscle differentiation
European Nucleotide Archive (ENA) accession number, PRJEB6112.

https://www.ebi.ac.uk/ena/browser/view/PRJEB6112
(2016) Gene expression profiling of human and murine in vitro muscle differentiation
Gene Expression Omnibus (GEO) accession number, GSE70389.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70389
(2015) Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells
FANTOM5 Consortium.

https://fantom.gsc.riken.jp/5/data/

Article and author information

Author details

Andrea Cipriano

Dept. of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le A. Moro 5, Rome, 00185, Italy; Present address: Dept. of Obstetrics & Gynecology, Stanford University, 94306 Stan, La Sapienza University of Rome, Rome, Italy

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0775-3198
Martina Macino

Dept. of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le A. Moro 5, Rome, 00185, Italy; Institute of Molecular Biology and Pathology (IBPM),, La Sapienza University of Rome, National Research Council (CNR), Rome, Italy

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8730-9005
Giulia Buonaiuto

Dept. of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy

Competing interests
The authors declare that no competing interests exist.
Tiziana Santini

Center for Life Nano Science, Viale Regina Elena 291, Rome, 00161, Italy, Istituto Italiano di Tecnologia, Rome, Italy

Competing interests
The authors declare that no competing interests exist.
Beatrice Biferali

Dept. of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le A. Moro 5, Rome, 00185, Italy; Institute of Molecular Biology and Pathology (IBPM),, La Sapienza University of Rome, National Research Council (CNR), Rome, Italy

Competing interests
The authors declare that no competing interests exist.
Giovanna Peruzzi

Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma, Italy

Competing interests
The authors declare that no competing interests exist.
Alessio Colantoni

Dept. of Biology and Biotechnology Charles Darwin, La Sapienza, University of Rome, Rome, Italy

Competing interests
The authors declare that no competing interests exist.
Chiara Mozzetta

Institute of Molecular Biology and Pathology (IBPM),, National Research Council (CNR) at Sapienza University of Rome, Rome, Italy

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7147-7266
Monica Ballarino

Biology and Biotechnology C. Darwin, La Sapienza University of Rome, Roma, Italy

For correspondence
monica.ballarino@uniroma1.it

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8595-7105

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

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.