BEATRICE BIFERALI

Dottoressa di ricerca

ciclo: XXXII



Titolo della tesi: H3K9 methylation controls Fibro-Adipogenic Progenitors identity and skeletal muscle repair

Fibro-Adipogenic Progenitors (FAPs) are crucial regulators of muscle homeostasis as they possess the intrinsic ability to either support muscle regeneration or to contribute to fibro-adipogenic degeneration of dystrophic muscles. Therefore, the elucidation of the molecular mechanisms controlling their phenotypical plasticity holds therapeutic potential. Here we provide evidence that FAPs are particularly enriched in histone H3 lysine K9 methyltransferases (H3K9 KMTs), G9a, GLP and Prdm16. Our data indicate that H3K9 KMTs safeguard FAPs identity by repressing alternative transcriptional programs through deposition of H3K9 di- methylation (H3K9me2). Specifically, we show that Prdm16 controls G9a/GLP-mediated deposition of H3K9me2 at muscle- specific loci. Of note, we found Prdm16, G9a and GLP particularly enriched at the nuclear lamina (NL) of FAPs, suggesting they organize heterochromatin at the nuclear periphery to maintain the stable repression of genes encoding alternative developmental regulators. Accordingly, pharmacological inhibition or RNAi- mediated knock-down (KD) of H3K9 KMTs de-repress master myogenic genes in FAPs and induce the muscle differentiation program. Together, our findings reveal a FAPs-specific epigenetic axis important to control their identity. These findings are important especially for the possible therapeutic application to conceive strategies aimed to reprogram FAPs fate in vivo to prevent degeneration of diseased muscles.

Produzione scientifica

  • 11573/1283719 - 2019 - Epigenetic Regulation of Muscle Stem Cells During Skeletal Muscle Regeneration and Disease (02a Capitolo o Articolo)
    BIFERALI, BEATRICE; MOZZETTA, CHIARA
  • 11573/1323383 - 2019 - Fibro–Adipogenic progenitors cross-talk in skeletal muscle: the social network (01g Articolo di rassegna (Review))
    BIFERALI, BEATRICE; PROIETTI, DAISY; MOZZETTA, CHIARA; MADARO, LUCA
  • 11573/1327261 - 2020 - Statins interfere with the attachment of S. cerevisiae mtDNA to the inner mitochondrial membrane (01a Articolo in rivista)
    CIRIGLIANO, ANGELA; AMELINA, ANTONIA; BIFERALI, BEATRICE; MACONE, ALBERTO; MOZZETTA, CHIARA; BIANCHI, MICHELE MARIA; MORI, MATTIA; BOTTA, BRUNO; NEGRI, RODOLFO; RINALDI, TERESA
  • 11573/1380567 - 2020 - H3K9 methylation controls Fibro-Adipogenic Progenitors identity and skeletal muscle repair (07a Tesi di Dottorato)
    BIFERALI, BEATRICE
  • 11573/1495885 - 2017 - Role of Histone H3 lysine 9 methyltransferases during Duchenne Muscular Dystrophy progression (01h Abstract in rivista)
    BIFERALI, BEATRICE; BIANCONI, VALERIA; MOZZETTA, CHIARA
  • 11573/1495879 - 2016 - Role of Histone H3 Lysine 9 (H3K9) methyltransferases G9a and GLP in the epigenetic regulation of Fibroadipogenic progenitors (FAPs) differentiation during Duchenne Muscular Dystrophy (DMD) progression (01h Abstract in rivista)
    BIANCONI, VALERIA; BIFERALI, BEATRICE; MOZZETTA, CHIARA
  • 11573/1556210 - 2021 - Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair (01a Articolo in rivista)
    BIFERALI, BEATRICE; BIANCONI, VALERIA; POLVERINO, FEDERICA; BIAGIONI, STEFANO; MOZZETTA, CHIARA
  • 11573/1477955 - 2021 - Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells (01a Articolo in rivista)
    CIPRIANO, ANDREA; MACINO, MARTINA; BUONAIUTO, GIULIA; SANTINI, TIZIANA; BIFERALI, BEATRICE; PERUZZI, GIOVANNA; COLANTONI, ALESSIO; MOZZETTA, CHIARA; BALLARINO, MONICA
  • 11573/1495882 - 2017 - Histone 3 lysine 9 methyltransferases G9a and GLP as potential pharmacological targets in skeletal muscle regeneration and Duchenne Muscular Dystrophy (01h Abstract in rivista)
    BIANCONI, VALERIA; BIFERALI, BEATRICE; MOZZETTA, CHIARA
  • 11573/1610527 - 2021 - Targeting the expression of long noncoding RNAs in murine satellite cells from single myofibers (01a Articolo in rivista)
    MACINO, MARTINA; BIFERALI, BEATRICE; CIPRIANO, ANDREA; BALLARINO, MONICA; MOZZETTA, CHIARA

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