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  1. Article ; Online: Long non-coding RNAs and their role in muscle regeneration.

    Biferali, Beatrice / Mocciaro, Emanuele / Runfola, Valeria / Gabellini, Davide

    Current topics in developmental biology

    2024  Volume 158, Page(s) 433–465

    Abstract: In mammals, most of the genome is transcribed to generate a large and heterogeneous variety of non-protein coding RNAs, that are broadly grouped according to their size. Long noncoding RNAs include a very large and versatile group of molecules. Despite ... ...

    Abstract In mammals, most of the genome is transcribed to generate a large and heterogeneous variety of non-protein coding RNAs, that are broadly grouped according to their size. Long noncoding RNAs include a very large and versatile group of molecules. Despite only a minority of them has been functionally characterized, there is emerging evidence indicating long noncoding RNAs as important regulators of expression at multiple levels. Several of them have been shown to be modulated during myogenic differentiation, playing important roles in the regulation of skeletal muscle development, differentiation and homeostasis, and contributing to neuromuscular diseases. In this chapter, we have summarized the current knowledge about long noncoding RNAs in skeletal muscle and discussed specific examples of long noncoding RNAs (lncRNAs and circRNAs) regulating muscle stem cell biology. We have also discussed selected long noncoding RNAs involved in the most common neuromuscular diseases.
    MeSH term(s) RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Animals ; Humans ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/physiology ; Regeneration/genetics ; Muscle Development/genetics ; Cell Differentiation
    Chemical Substances RNA, Long Noncoding
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ISSN 1557-8933 ; 0070-2153
    ISSN (online) 1557-8933
    ISSN 0070-2153
    DOI 10.1016/bs.ctdb.2024.02.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: DUX4-r exerts a neomorphic activity that depends on GTF2I in acute lymphoblastic leukemia.

    Campolungo, Daniele / Salomé, Mara / Biferali, Beatrice / Tascini, Anna Sofia / Gabellini, Davide

    Science advances

    2023  Volume 9, Issue 37, Page(s) eadi3771

    Abstract: Translocations producing rearranged versions of the transcription factor double homeobox 4 (DUX4-r) are one of the most frequent causes of B cell acute lymphoblastic leukemia (B-ALL). DUX4-r retains the DNA binding domain of wild-type DUX4 but is ... ...

    Abstract Translocations producing rearranged versions of the transcription factor double homeobox 4 (DUX4-r) are one of the most frequent causes of B cell acute lymphoblastic leukemia (B-ALL). DUX4-r retains the DNA binding domain of wild-type DUX4 but is truncated on the C-terminal transcription activation domain. The precise mechanism through which DUX4-r causes leukemia is unknown, and no targeted therapy is currently available. We found that the rearrangement leads to both a loss and a gain of function in DUX4-r. Loss of CBP/EP300 transcriptional coactivator interaction leads to an inability to bind and activate repressed chromatin. Concurrently, a gain of interaction with the general transcription factor 2 I (GTF2I) redirects DUX4-r toward leukemogenic targets. This neomorphic activity exposes an Achilles' heel whereby DUX4-r-positive leukemia cells are exquisitely sensitive to GTF2I targeting, which inhibits DUX4-r leukemogenic activity. Our work elucidates the molecular mechanism through which DUX4-r causes leukemia and suggests a possible therapeutic avenue tailored to this B-ALL subtype.
    MeSH term(s) Humans ; Antibodies ; Chromatin ; Gene Rearrangement ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Transcription Factors ; Transcription Factors, TFII ; Transcription Factors, TFIII
    Chemical Substances Antibodies ; Chromatin ; GTF2I protein, human ; Transcription Factors ; Transcription Factors, TFII ; Transcription Factors, TFIII ; DUX4L1 protein, human
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adi3771
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Targeting the Expression of Long Noncoding RNAs in Murine Satellite Cells from Single Myofibers.

    Macino, Martina / Biferali, Beatrice / Cipriano, Andrea / Ballarino, Monica / Mozzetta, Chiara

    Bio-protocol

    2021  Volume 11, Issue 21, Page(s) e4209

    Abstract: LncRNAs have been recently implicated in the epigenetic control of muscle differentiation and their functional characterization has traditionally relied ... ...

    Abstract LncRNAs have been recently implicated in the epigenetic control of muscle differentiation and their functional characterization has traditionally relied upon
    Language English
    Publishing date 2021-11-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325 ; 2331-8325
    ISSN (online) 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.4209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Fibro-Adipogenic Progenitors Cross-Talk in Skeletal Muscle: The Social Network.

    Biferali, Beatrice / Proietti, Daisy / Mozzetta, Chiara / Madaro, Luca

    Frontiers in physiology

    2019  Volume 10, Page(s) 1074

    Abstract: Skeletal muscle is composed of a large and heterogeneous assortment of cell populations that interact with each other to maintain muscle homeostasis and orchestrate regeneration. Although satellite cells (SCs) - which are muscle stem cells - are the ... ...

    Abstract Skeletal muscle is composed of a large and heterogeneous assortment of cell populations that interact with each other to maintain muscle homeostasis and orchestrate regeneration. Although satellite cells (SCs) - which are muscle stem cells - are the protagonists of functional muscle repair following damage, several other cells such as inflammatory, vascular, and mesenchymal cells coordinate muscle regeneration in a finely tuned process. Fibro-adipogenic progenitors (FAPs) are a muscle interstitial mesenchymal cell population, which supports SCs differentiation during tissue regeneration. During the first days following muscle injury FAPs undergo massive expansion, which is followed by their macrophage-mediated clearance and the re-establishment of their steady-state pool. It is during this critical time window that FAPs, together with the other cellular components of the muscle stem cell niche, establish a dynamic network of interactions that culminate in muscle repair. A number of different molecules have been recently identified as important mediators of this cross-talk, and its alteration has been associated with different muscle pathologies. In this review, we will focus on the soluble factors that regulate FAPs activity, highlighting their roles in orchestrating the inter-cellular interactions between FAPs and the other cell populations that participate in muscle regeneration.
    Language English
    Publishing date 2019-08-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2019.01074
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Epigenetic regulation of

    Cipriano, Andrea / Macino, Martina / Buonaiuto, Giulia / Santini, Tiziana / Biferali, Beatrice / Peruzzi, Giovanna / Colantoni, Alessio / Mozzetta, Chiara / Ballarino, Monica

    eLife

    2021  Volume 10

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Animals ; Epigenesis, Genetic ; Female ; Gene Expression Regulation ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle Development/genetics ; Muscle, Skeletal/growth & development ; Muscle, Skeletal/metabolism ; Myoblasts/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
    Chemical Substances RNA, Long Noncoding
    Language English
    Publishing date 2021-01-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.54782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair.

    Biferali, Beatrice / Bianconi, Valeria / Perez, Daniel Fernandez / Kronawitter, Sophie Pöhle / Marullo, Fabrizia / Maggio, Roberta / Santini, Tiziana / Polverino, Federica / Biagioni, Stefano / Summa, Vincenzo / Toniatti, Carlo / Pasini, Diego / Stricker, Sigmar / Di Fabio, Romano / Chiacchiera, Fulvio / Peruzzi, Giovanna / Mozzetta, Chiara

    Science advances

    2021  Volume 7, Issue 23

    Abstract: H3K9 methylation maintains cell identity orchestrating stable silencing and anchoring of alternate fate genes within the heterochromatic compartment underneath the nuclear lamina (NL). However, how cell type-specific genomic regions are specifically ... ...

    Abstract H3K9 methylation maintains cell identity orchestrating stable silencing and anchoring of alternate fate genes within the heterochromatic compartment underneath the nuclear lamina (NL). However, how cell type-specific genomic regions are specifically targeted to the NL is still elusive. Using fibro-adipogenic progenitors (FAPs) as a model, we identified Prdm16 as a nuclear envelope protein that anchors H3K9-methylated chromatin in a cell-specific manner. We show that Prdm16 mediates FAP developmental capacities by orchestrating lamina-associated domain organization and heterochromatin sequestration at the nuclear periphery. We found that Prdm16 localizes at the NL where it cooperates with the H3K9 methyltransferases G9a/GLP to mediate tethering and silencing of myogenic genes, thus repressing an alternative myogenic fate in FAPs. Genetic and pharmacological disruption of this repressive pathway confers to FAP myogenic competence, preventing fibro-adipogenic degeneration of dystrophic muscles. In summary, we reveal a druggable mechanism of heterochromatin perinuclear sequestration exploitable to reprogram FAPs in vivo.
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abd9371
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Statins interfere with the attachment of

    Cirigliano, Angela / Amelina, Antonia / Biferali, Beatrice / Macone, Alberto / Mozzetta, Chiara / Bianchi, Michele Maria / Mori, Mattia / Botta, Bruno / Pick, Elah / Negri, Rodolfo / Rinaldi, Teresa

    Journal of enzyme inhibition and medicinal chemistry

    2019  Volume 35, Issue 1, Page(s) 129–137

    Abstract: The 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme of the mevalonate pathway for the synthesis of cholesterol in mammals (ergosterol in fungi), is inhibited by statins, a class of cholesterol lowering drugs. Indeed, statins are in a wide medical ... ...

    Abstract The 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme of the mevalonate pathway for the synthesis of cholesterol in mammals (ergosterol in fungi), is inhibited by statins, a class of cholesterol lowering drugs. Indeed, statins are in a wide medical use, yet statins treatment could induce side effects as hepatotoxicity and myopathy in patients. We used
    MeSH term(s) DNA, Mitochondrial/chemistry ; DNA, Mitochondrial/metabolism ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism ; Mitochondria/metabolism ; Mitochondrial Membranes/chemistry ; Mitochondrial Membranes/metabolism ; Saccharomyces cerevisiae/chemistry
    Chemical Substances DNA, Mitochondrial ; Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Language English
    Publishing date 2019-11-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2082578-X
    ISSN 1475-6374 ; 1475-6366
    ISSN (online) 1475-6374
    ISSN 1475-6366
    DOI 10.1080/14756366.2019.1687461
    Database MEDical Literature Analysis and Retrieval System OnLINE

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