ATP Citrate Lyase Regulates Myofiber Differentiation and Increases Regeneration by Altering Histone Acetylation
| Autor: | Pascale Brebbia, Giulia Minetti, Gauthier Toussaint, Peter Kahle, Frederic Morvan, Benjamin Jourde, Suman K. Das, Giulio Morozzi, David J. Glass, Mara Fornaro, Helene Rivet |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Satellite Cells Skeletal Muscle Transcription Genetic ATP citrate lyase Primary Cell Culture Muscle Development MyoD Cardiotoxins Article General Biochemistry Genetics and Molecular Biology Histones Mice 03 medical and health sciences medicine Animals Humans Regeneration Myocyte Gene silencing skeletal muscle Muscle Skeletal lcsh:QH301-705.5 MyoD Protein satellite cells biology Myogenesis Chemistry histone acetylation Skeletal muscle Acetylation Cell Differentiation musculoskeletal system Mitochondria Cell biology Mice Inbred C57BL 030104 developmental biology Histone medicine.anatomical_structure Gene Expression Regulation lcsh:Biology (General) ATP Citrate (pro-S)-Lyase IGF-1 biology.protein Signal Transduction |
| Zdroj: | Cell Reports, Vol 21, Iss 11, Pp 3003-3011 (2017) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2017.11.038 |
| Popis: | Summary ATP citrate lyase (ACL) plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. We report here that ACL silencing impairs myoblast and satellite cell (SC) differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD. Conversely, overexpression of ACL enhances MYOD levels and promotes myogenesis. Myogenesis is dependent on transcriptional but also other mechanisms. We show that ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression. ACL overexpression in murine skeletal muscle leads to improved regeneration after cardiotoxin-mediated damage. Thus, our findings suggest a mechanism for regulating SC differentiation and enhancing regeneration, which might be exploited for devising therapeutic approaches for treating skeletal muscle disease. |
| Databáze: | OpenAIRE |
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