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Journal articles
Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC-MEF2 complexes.
Angela Nebbioso
1
Fabio Manzo
1, 2
Marco Miceli
1
Mariarosaria Conte
1
Lucrezia Manente
3
Alfonso Baldi
4
Antonio de Luca
5
Dante Rotili
6
Sergio Valente
6
Antonello Mai
6
Alessandro Usiello
7, 8
Hinrich Gronemeyer
2
Lucia Altucci
1
Sergio Valente 6
Author
Antonello Mai 6
Author
Alessandro Usiello 7, 8
Author
Hinrich Gronemeyer 2
Author
Lucia Altucci 1
Author
1
Dipartimento di Patologia Generale (Napoli - Italy)
- Seconda Università degli studi di Napoli (Piazza Luigi Miraglia, 2 – 80138 NAPOLI - Italy)
2
IGBMC - Institut de génétique et biologie moléculaire et cellulaire (I.G.B.M.C, Parc D'Innovation 1 Rue Laurent Fries - BP 10142 67404 ILLKIRCH CEDEX - France)
- Université Louis Pasteur - Strasbourg I (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U596 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7104 (France)
3
Laboratory C (Regina Elena, Roma - Italy)
- Regina Elena (France)
- Department for the Development of Therapeutic Programs (France)
4
Dipartimento di Biochimica e Biofisica (Vico Luigi de Crecchio 7, Napoli - Italy)
- Seconda Universita di Napoli (France)
5
Istituto di Anatomia Topografica (Vico Luigi de Crecchio 7, Napoli - Italy)
- Seconda Universita di Napoli (France)
6
Dipartimento di Studi Farmaceutici (Roma - Italy)
- Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti (Université de Rome La Sapienza 5 Place Aldo Moro 00185 Rome - Italy)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
- Università degli Studi di Roma "La Sapienza" [Rome] (Piazzale Aldo Moro 5, 00185 Roma - Italy)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
Abstract : Histone deacetylase (HDAC) inhibitors are promising new epi-drugs, but the presence of both class I and class II enzymes in HDAC complexes precludes a detailed elucidation of the individual HDAC functions. By using the class II-specific HDAC inhibitor MC1568, we separated class I- and class II-dependent effects and defined the roles of class II enzymes in muscle differentiation in cultured cells and in vivo. MC1568 arrests myogenesis by (i) decreasing myocyte enhancer factor 2D (MEF2D) expression, (ii) by stabilizing the HDAC4-HDAC3-MEF2D complex, and (iii) paradoxically, by inhibiting differentiation-induced MEF2D acetylation. In vivo MC1568 shows an apparent tissue-selective HDAC inhibition. In skeletal muscle and heart, MC1568 inhibits the activity of HDAC4 and HDAC5 without affecting HDAC3 activity, thereby leaving MEF2-HDAC complexes in a repressed state. Our results suggest that HDAC class II-selective inhibitors might have a therapeutic potential for the treatment of muscle and heart diseases.
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Journal articles
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https://www.hal.inserm.fr/inserm-00420167
Contributor : Maité Peney <>
Submitted on : Monday, September 28, 2009 - 1:15:08 PM
Last modification on : Thursday, April 23, 2020 - 2:26:26 PM
Contributor : Maité Peney <>
Submitted on : Monday, September 28, 2009 - 1:15:08 PM
Last modification on : Thursday, April 23, 2020 - 2:26:26 PM
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- HAL Id : inserm-00420167, version 1
- DOI : 10.1038/embor.2009.88
- PUBMED : 19498465
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CNRS | RIIP | IGBMC | SITE-ALSACE
Citation
Angela Nebbioso, Fabio Manzo, Marco Miceli, Mariarosaria Conte, Lucrezia Manente, et al.. Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC-MEF2 complexes.. EMBO Reports, EMBO Press, 2009, 10 (7), pp.776-82. ⟨10.1038/embor.2009.88⟩. ⟨inserm-00420167⟩
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