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TNF/p38 alpha/Polycomb Signaling to Pax7 Locus in Satellite Cells Links Inflammation to the Epigenetic Control of Muscle Regeneration

  1. Author:
    Palacios, D.
    Mozzetta, C.
    Consalvi, S.
    Caretti, G.
    Saccone, V.
    Proserpio, V.
    Marquez, V. E.
    Valente, S.
    Mai, A.
    Forcales, S. V.
    Sartorelli, V.
    Puri, P. L.

  2. Author Address

    [Palacios, Daniela; Mozzetta, Chiara; Consalvi, Silvia; Saccone, Valentina; Puri, Pier Lorenzo] IRCCS Fdn Santa Lucia, DTI, I-00143 Rome, Italy. [Palacios, Daniela; Mozzetta, Chiara; Consalvi, Silvia; Saccone, Valentina; Puri, Pier Lorenzo] European Brain Res Inst, I-00143 Rome, Italy. [Palacios, Daniela; Mozzetta, Chiara; Consalvi, Silvia; Saccone, Valentina; Puri, Pier Lorenzo] Sanford Burnham Inst Med Res, La Jolla, CA 92037 USA. [Caretti, Giuseppina; Proserpio, Valentina; Sartorelli, Vittorio] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. [Caretti, Giuseppina; Proserpio, Valentina] Univ Milan, Dept Biomol Sci & Biotechnol, I-20133 Milan, Italy. [Marquez, Victor E.] NCI, Med Chem Lab, Frederick, MD 21720 USA. [Valente, Sergio; Mai, Antonello] Univ Roma La Sapienza, Dept Chem & Drug Technol, Inst Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy.;Puri, PL, IRCCS Fdn Santa Lucia, DTI, I-00143 Rome, Italy.;plpuri@dti.telethon.it
    1. Year: 2010
    2. Date: Oct
  2. Journal: Cell Stem Cell
    1. 7
    2. 4
    3. Pages: 455-469
  4. Type of Article: Article
  5. ISSN: 1934-5909
  1. Abstract:

    How regeneration cues are converted into the epigenetic information that controls gene expression in adult stem cells is currently unknown. We identified an inflammation-activated signaling in muscle stem (satellite) cells, by which the polycomb repressive complex 2 (PRC2) represses Pax7 expression during muscle regeneration. TNF-activated p38 alpha kinase promotes the interaction between YY1 and PRC2, via threonine 372 phosphorylation of EZH2, the enzymatic subunit of the complex, leading to the formation of repressive chromatin on Pax7 promoter. TNF-alpha antibodies stimulate satellite cell proliferation in regenerating muscles of dystrophic or normal mice. Genetic knockdown or pharmacological inhibition of the enzymatic components of the p38/PRC2 signaling-p38 alpha and EZH2-invariably promote Pax7 expression and expansion of satellite cells that retain their differentiation potential upon signaling resumption. Genetic knockdown of Pax7 impaired satellite cell proliferation in response to p38 inhibition, thereby establishing the biological link between p38/PRC2 signaling to Pax7 and satellite cell decision to proliferate or differentiate.

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External Sources

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  2. DOI: 10.1016/j.stem.2010.08.013
  3. View record in Web of Science®
  4. WOS: 000283270600008

Library Notes

  1. Fiscal Year: FY2010-2011
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