Department
neurobiology
Document Type
Article
Abstract
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder causing progressive muscle degeneration. Although cardiomyopathy is a leading mortality cause in DMD patients, the mechanisms underlying heart failure are not well understood. Previously, we showed that NF-κB exacerbates DMD skeletal muscle pathology by promoting inflammation and impairing new muscle growth. Here, we show that NF-κB is activated in murine dystrophic (mdx) hearts, and that cardiomyocyte ablation of NF-κB rescues cardiac function. This physiological improvement is associated with a signature of upregulated calcium genes, coinciding with global enrichment of permissive H3K27 acetylation chromatin marks and depletion of the transcriptional repressors CCCTC-binding factor, SIN3 transcription regulator family member A, and histone deacetylase 1. In this respect, in DMD hearts, NF-κB acts differently from its established role as a transcriptional activator, instead promoting global changes in the chromatin landscape to regulate calcium genes and cardiac function.
Publication Date
12-1-2018
Publication Title
Nature Communications
ISSN
20411723
Volume
9
Issue
1
Digital Object Identifier (DOI)
10.1038/s41467-018-05910-1
Recommended Citation
Peterson, Jennifer M.; Wang, David J.; Shettigar, Vikram; Roof, Steve R.; Canan, Benjamin D.; Bakkar, Nadine; Shintaku, Jonathan; Gu, Jin Mo; Little, Sean C.; Ratnam, Nivedita M.; Londhe, Priya; Lu, Leina; Gaw, Christopher E.; Petrosino, Jennifer M.; Liyanarachchi, Sandya; Wang, Huating; Janssen, Paul M.L.; Davis, Jonathan P.; Ziolo, Mark T.; Sharma, Sudarshana M.; and Guttridge, Denis C., "Nf-κb Inhibition Rescues Cardiac Function By Remodeling Calcium Genes In A Duchenne Muscular Dystrophy Model" (2018). Translational Neuroscience. 3.
https://scholar.barrowneuro.org/neurobiology/3