Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy Export

@article{citeulike:4275432, abstract = {The present study provides evidence that abnormal patterns of global histone modification are present in the skeletal muscle nuclei of mdx mice and Duchenne muscular dystrophy (DMD) patients. A combination of specific histone H3 modifications, including Ser-10 phosphorylation, acetylation of Lys 9 and 14, and Lys 79 methylation, were found enriched in muscle biopsies from human patients affected by DMD and in late-term fetuses, early postnatal pups, or adult mdx mice. In this context, chromatin immunoprecipitation experiments showed an enrichment of these modifications at the loci of genes involved in proliferation or inflammation, suggesting a regulatory effect on gene expression. Remarkably, the reexpression of dystrophin induced by gentamicin treatment or the administration of nitric oxide (NO) donors reversed the abnormal pattern of H3 histone modifications. These findings suggest an unanticipated link between the dystrophin-activated NO signaling and the remodeling of chromatin. In this context, the regulation of class IIa histone deacetylases (HDACs) 4 and 5 was found altered as a consequence of the reduced NO-dependent protein phosphatase 2A activity, indicating that both NO and class IIa HDACs are important for satellite cell differentiation and gene expression in mdx mice. In conclusion, this work provides the first evidence of a role for NO as an epigenetic regulator in DMD.--Colussi, C., Gurtner, A., Rosati, J., Illi, B., Ragone, G., Piaggio, G., Moggio, M., Lamperti, C., D'Angelo, G., Clementi, E., Minetti, G., Mozzetta, C., Antonini, A., Capogrossi, M. C., Puri, P. L., Gaetano, C. Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy. 10.1096/fj.08-115618}, author = {Colussi, Claudia and Gurtner, Aymone and Rosati, Jessica and Illi, Barbara and Ragone, Gianluca and Piaggio, Giulia and Moggio, Maurizio and Lamperti, Costanza and D'Angelo, Grazia and Clementi, Emilio and Minetti, Giulia and Mozzetta, Chiara and Antonini, Annalisa and Capogrossi, Maurizio C. and Puri, Pier L. and Gaetano, Carlo}, citeulike-article-id = {4275432}, citeulike-linkout-0 = {http://dx.doi.org/10.1096/fj.08-115618}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19264835}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19264835}, day = {2}, doi = {10.1096/fj.08-115618}, journal = {FASEB J.}, keywords = {chromatin, disease, epigenetics}, month = {April}, pages = {fj.08-115618+}, posted-at = {2009-04-05 11:06:09}, priority = {2}, title = {Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy}, url = {http://dx.doi.org/10.1096/fj.08-115618}, year = {2009} }

TY - JOUR ID - citeulike:4275432 L3 - citeulike-article-id:4275432 N2 - The present study provides evidence that abnormal patterns of global histone modification are present in the skeletal muscle nuclei of mdx mice and Duchenne muscular dystrophy (DMD) patients. A combination of specific histone H3 modifications, including Ser-10 phosphorylation, acetylation of Lys 9 and 14, and Lys 79 methylation, were found enriched in muscle biopsies from human patients affected by DMD and in late-term fetuses, early postnatal pups, or adult mdx mice. In this context, chromatin immunoprecipitation experiments showed an enrichment of these modifications at the loci of genes involved in proliferation or inflammation, suggesting a regulatory effect on gene expression. Remarkably, the reexpression of dystrophin induced by gentamicin treatment or the administration of nitric oxide (NO) donors reversed the abnormal pattern of H3 histone modifications. These findings suggest an unanticipated link between the dystrophin-activated NO signaling and the remodeling of chromatin. In this context, the regulation of class IIa histone deacetylases (HDACs) 4 and 5 was found altered as a consequence of the reduced NO-dependent protein phosphatase 2A activity, indicating that both NO and class IIa HDACs are important for satellite cell differentiation and gene expression in mdx mice. In conclusion, this work provides the first evidence of a role for NO as an epigenetic regulator in DMD.--Colussi, C., Gurtner, A., Rosati, J., Illi, B., Ragone, G., Piaggio, G., Moggio, M., Lamperti, C., D'Angelo, G., Clementi, E., Minetti, G., Mozzetta, C., Antonini, A., Capogrossi, M. C., Puri, P. L., Gaetano, C. Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy. 10.1096/fj.08-115618 JF - FASEB J. TI - Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy SP - fj.08-115618 KW - chromatin KW - disease KW - epigenetics AU - Colussi, Claudia AU - Gurtner, Aymone AU - Rosati, Jessica AU - Illi, Barbara AU - Ragone, Gianluca AU - Piaggio, Giulia AU - Moggio, Maurizio AU - Lamperti, Costanza AU - D'Angelo, Grazia AU - Clementi, Emilio AU - Minetti, Giulia AU - Mozzetta, Chiara AU - Antonini, Annalisa AU - Capogrossi, Maurizio AU - Puri, Pier AU - Gaetano, Carlo PY - 2009/04/02/ UR - http://dx.doi.org/10.1096/fj.08-115618 ER -