Fax :
chiara.mozzetta@uniroma1.it
Researcher
Istitute of Molecular Biology and Pathology - National Research Council
Department of Biology and Biotecnology - Charles Darwin
Sapienza University of Rome - General Physiology Building \u2013 ground floor, lab 10 - P.le A.Moro 5, 00185 Rome
Epigenetic regulation of muscle progenitor cells during skeletal muscle regeneration and disease
The research in my lab aims to dissect the epigenetic mechanisms governing muscle progenitor cells’ fate determination. We are interested in studying how histone modifying enzymes control stem cells’ alternative transcriptional programs and fates. We aim to reveal how these epigenetic players control skeletal muscle differentiation/regeneration, with the goal to understand how these processes are deregulated in muscle disorders, such as muscular dystrophies and malignancies of muscular origin as rhabdomyosarcomas.
In particular, in my lab we aim to:
- understand the role of H3K9 methyltransferases in dictating cell fates decision in muscle stem cells and fibro-adipogenic progenitors, during skeletal muscle regeneration and degeneration.
- elucidate the epigenetic basis of rhabdomyosarcoma (RMS), with an emphasis in deciphering the molecular and cellular mechanism underlying the incapacity of RMS to undergo terminal differentiation
- dissect the mechanism through which histone methyltransferases are selectively targeted to defined chromatin loci .
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• Mozzetta C. Isolation and culture of muscle stem cells. Methods Mol Biol. 2016; 1480:311-22. doi: 10.1007/978-1-4939-6380-5_27.
• Cesarini E, Mozzetta C, Marullo F, Gregoretti F, Gargiulo A, Columbaro M, Cortesi A, Antonelli L, Di Pelino S, Squarzoni S, Palacios D, Zippo A, Bodega B, Oliva G, Lanzuolo C. Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes. J Cell Biol. 2015 Nov 9;211(3):533-51. doi: 10.1083/jcb.201504035. • Mozzetta C*, Boyarchuk E, Pontis J, Ait-Si-Ali S,*. Sound of Silence: The properties and functions of repressive lysine methyltransferases. Nature Review Molecular Cell Biology. 2015 Aug;16(8):499-513. doi: 10.1038/nrm4029. Review. * corresponding author. • Mozzetta C*, Pontis J, Ait-Si-Ali S,*. Functional crosstalks between lysine methyltransferases on histone substrates: the case of G9a/GLP and PRC2. Invited review Antioxidant & Redox Signaling, special issue on Epigenetics. 2014 Nov 3* corresponding author • Consalvi S, Saccone V, Mozzetta C*. Histone Deacetylase Inhibitors (HDACi): the potential of an epigenetic treatment for Duchenne Muscular Dystrophy. Invited review. 2014;6(5):547-60. doi: 10.2217/epi.14.36. Epigenomics. • Saccone V, Consalvi S, Giordani L, Mozzetta C, Ryan T, Madaro L, Rojas Munoz A, Bruneau B, Fasanaro P, Termanini A, Barozzi I, Mercola M, Minucci S, Puri P.L. (2014) HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibroadipogenic progenitors in dystrophic muscles. Genes & Development, Apr 15;28(8):841-57. doi: 10.1101/gad.234468.113.
• Mozzetta C, Pontis J, Fritsch L, Robin P, Portoso M, Proux C, Margueron R, Ait-Si-Ali S (2014). The Histone H3 Lysine 9 Methyltransferases G9a and GLP Regulate Polycomb Repressive Complex 2-Mediated Gene Silencing. Molecular Cell. Jan 23;53(2):277-89. doi: 10.1016/j.molcel.2013.12.005. Epub 2014 Jan 2. • Consalvi S, Mozzetta C, Bettica P, Germani M, Fiorentini F, Del Bene F, Rocchetti M, Leoni F, Monzani V, Mascagni P, Puri PL, Saccone V. (2013). Preclinical studies in the mdx mouse model of duchenne muscular dystrophy with the histone deacetylase inhibitor givinostat. Molecular medicine (Cambridge, Mass.), 19, 79–87. doi:10.2119/molmed.2013.00011 • Mozzetta C, Consalvi S, Saccone V, Tierney M, Diamantini A, Mitchell KJ, Marazzi G, Borsellino G, Battistini L, Sassoon D, Sacco A, Puri PL. (2013). Fibroadipogenic progenitors mediate the ability of HDAC inhibitors to promote regeneration in dystrophic muscles of young, but not old Mdx mice. EMBO Molecular Medicine, 5, 626–39. doi:10.1002/emmm.201202096. • Mozzetta, C., Consalvi, S., Saccone, V., Forcales, S. V, Puri, P. L., & Palacios, D. Selective control of Pax7 expression by TNF-activated p38a/polycomb repressive complex 2 (PRC2) signaling during muscle satellite cell differentiation. Cell cycle (2011) 10, 191–198. doi:10.4161/cc.10.2.14441. • Palacios, D.*, Mozzetta, C.*, Consalvi, S., Caretti, G., Saccone, V., Proserpio, V., Marquez SV., Valente S., Mai A., Forcale SV., Sartorelli V., Puri, P. L. (2010). TNF/p38a/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration. Cell Stem Cell, 7, 455–469. doi:10.1016/j.stem.2010.08.013. * equal contribution |
- Dr. Beatrice Biferali (PhD student, Cell and Developmental Biology course; Dept. Biology and Biotechnology “C. Darwin”, University Sapienza)
- Dr. Valeria Bianconi (PhD student, Cell and Developmental Biology course; Dept. Biology and Biotechnology “C. Darwin”, University Sapienza) - Dr. Alberto Gualtieri (Post-Doc; Dept. Biology and Biotechnology “C. Darwin”, University Sapienza) - Dr. Fabrizia Marullo (Post-Doc; Dept. Biology and Biotechnology “C. Darwin”, University Sapienza) |
- Dr. Giovanna Peruzzi (FACS sorting facility @ Italian Institute of Technology (IIT), Rome)
- Dr. Tiziana Santini (FACS sorting facility @ Italian Institute of Technology (IIT), Rome) - Prof. Francesca Grassi (Dept. Physiology and Pharmacology, Sapienza University of Rome) - Dr. Monica Ballarino (Dept. Biology and Biotechnology, Sapienza University of Rome) - Prof. Sigmar Stricker (Freie Universitat, Berlin, Germany) |
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