Signaling to the chromatin during skeletal myogenesis: novel targets for pharmacological modulation of gene expression.

Laboratory of Gene Expression, Dulbecco Telethon Institute (DTI) at Fondazione A. Cesalpino, ICBTE, San Raffaele Biomedical Science Park of Rome, Rome, Italy.
Seminars in Cell and Developmental Biology (Impact Factor: 5.97). 08/2005; 16(4-5):596-611. DOI: 10.1016/j.semcdb.2005.07.005
Source: PubMed

ABSTRACT Cellular differentiation entails an extensive reprogramming of the genome toward the expression of discrete subsets of genes, which establish the tissue-specific phenotype. This program is achieved by epigenetic marks of the chromatin at particular loci, and is regulated by environmental cues, such as soluble factors and cell-to-cell interactions. How the intracellular cascades convert the myriad of external stimuli into the nuclear information necessary to reprogram the genome toward specific responses is a question of biological and medical interest. The elucidation of the signaling converting cues from outside the cells into chromatin modifications at individual promoters holds the promise to unveil the targets for selective pharmacological interventions to modulate gene expression for therapeutic purposes. Enhancing muscle regeneration and preventing muscle breakdown are important goals in the therapy of muscular diseases, cancer-associated cachexia and aging-associated sarcopenia. We will summarize the recent progress of our knowledge of the regulation of gene expression by intracellular cascades elicited by external cues during skeletal myogenesis. And will illustrate the potential importance of targeting the chromatin signaling in regenerative medicine--e.g. to boost muscle regeneration.


Available from: Sonia Forcales, Jun 03, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: There has been great interest in the high-order harmonic generation (HHG) in gases as sources of novel tools for high photon energy pump-probe experiment (≈100 eV) with a great temporal resolution (
    Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS 01/1997; 2. DOI:10.1109/LEOS.1997.645547
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurons, astrocytes and oligodendrocytes arise from central nervous system (CNS) progenitor cells at defined times and locations during development, with transcription factors serving as key determinant of these different neural cell fates. An emerging theme is that the transcription factors that specify CNS cell fates function in a context-dependent manner, regulated by post-translational modifications and epigenetic alterations that partition the genome (and hence target genes) into active or silent domains. Here we profile the critical roles of the proneural genes, which encode basic-helix-loop-helix (bHLH) transcription factors, in specifying neural cell identities in the developing neocortex. In particular, we focus on the proneural genes Neurogenin 1 (Neurog1), Neurog2 and Achaete scute-like 1 (Ascl1), which are each expressed in a distinct fashion in the progenitor cell pools that give rise to all of the neuronal and glial cell types of the mature neocortex. Notably, while the basic functions of these proneural genes have been elucidated, it is becoming increasingly evident that tight regulatory controls dictate when, where and how they function. Current efforts to better understand how proneural gene function is regulated will not only improve our understanding of neocortical development, but are also critical to the future development of regenerative therapies for the treatment of neuronal degeneration or disease.
    Neuroscience 08/2013; 253. DOI:10.1016/j.neuroscience.2013.08.029 · 3.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: :Skeletal muscles harbor a resident population of stem cells termed satellite cells (SC). After trauma, SCs leave their quiescent state to enter the cell-cycle and undergo multiple rounds of proliferation, a process regulated by MyoD. To initiate differentiation, fusion and maturation to new skeletal muscle fibers, SCs upregulate myogenin. However, the regulation of these myogenic factors is not fully understood. In this study we demonstrate that Nrf2, a major regulator of oxidative stress defense, plays a role in the expression of these myogenic factors. Both in promoter studies with myoblasts and in a mouse model of muscle injury in Nrf2-deficient mice, we show that Nrf2 prolongs SC proliferation by up-regulating MyoD and suppresses SC differentiation by down-regulating myogenin. Moreover, we show that IL-6 and HGF, both factors that facilitate SC activation, induce Nrf2 activity in myoblasts. Thus Nrf2 activity promotes muscle regeneration by modulating SC proliferation and differentiation and thereby provides implications for tissue regeneration.
    The Journal of Pathology 12/2014; 234(4). DOI:10.1002/path.4418 · 7.33 Impact Factor