Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy; Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) at Sapienza University of Rome, Rome, Italy
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy
Tiziana Santini
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy; Center for Life Nano Science at Sapienza, Istituto Italiano di Tecnologia, Rome, Italy
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy; Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) at Sapienza University of Rome, Rome, Italy
Giovanna Peruzzi
Center for Life Nano Science at Sapienza, Istituto Italiano di Tecnologia, Rome, Italy
Alessio Colantoni
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy
Skeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cell (MuSC) activity. This ability requires the proper balance between MuSC expansion and differentiation, which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated long noncoding RNA (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 MuSC 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.
