Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC-MEF2 complexes. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue EMBO Reports Année : 2009

Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC-MEF2 complexes.

Résumé

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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Origine : Publication financée par une institution
Licence : CC BY - Paternité
Licence : CC BY - Paternité

Dates et versions

inserm-00420167 , version 1 (17-02-2023)

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Paternité

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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, 2009, 10 (7), pp.776-82. ⟨10.1038/embor.2009.88⟩. ⟨inserm-00420167⟩
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