Histone acetyltransferase inhibition rescues differentiation of emerin‐deficient myogenic progenitors
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 (H...
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Published in | Muscle & nerve Vol. 62; no. 1; pp. 128 - 136 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.07.2020
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | Funding information National Institutes of Health, Grant/Award Number: R15AR069935; National Institute of Arthritis and Musculoskeletal and Skin Diseases, Grant/Award Number: 2R15AR069935 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0148-639X 1097-4598 |
DOI: | 10.1002/mus.26892 |