Histone acetyltransferase inhibition rescues differentiation of emerin‐deficient myogenic progenitors
| Autor: | Katherine A. Bossone, Joseph A. Ellis, James M. Holaska |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Emerin 030105 genetics & heredity Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Physiology (medical) medicine Animals Muscular dystrophy Cells Cultured Histone Acetyltransferases Mice Knockout biology Sirtuin 1 Stem Cells Cell Differentiation Histone acetyltransferase medicine.disease HDAC3 Muscular Dystrophy Emery-Dreifuss Cell biology Mice Inbred C57BL Thiazoles Histone Acetylation biology.protein Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Muscle Nerve |
| ISSN: | 1097-4598 0148-639X |
| DOI: | 10.1002/mus.26892 |
| Popis: | Introduction Emery-Dreifuss muscular dystrophy (EDMD) is a disease characterized by skeletal muscle wasting, major tendon contractures, and cardiac conduction defects. Mutations in the gene encoding emerin cause EDMD1. Our previous studies suggested that emerin activation of histone deacetylase 3 (HDAC3) to reduce histone 4-lysine 5 (H4K5) acetylation (ac) is important for myogenic differentiation. Methods Pharmacological inhibitors (Nu9056, L002) of histone acetyltransferases targeting acetylated H4K5 were used to test whether increased acetylated H4K5 was responsible for the impaired differentiation seen in emerin-deficient myogenic progenitors. Results Nu9056 and L002 rescued impaired differentiation in emerin deficiency. SRT1720, which inhibits the nicotinamide adenine dinucleotide (NAD)+ -dependent deacetylase sirtuin 1 (SIRT1), failed to rescue myotube formation. Discussion We conclude that emerin regulation of HDAC3 activity to affect H4K5 acetylation dynamics is important for myogenic differentiation. Targeting H4K5ac dynamics represents a potential new strategy for ameliorating the skeletal muscle wasting seen in EDMD1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text