Histone Demethylase KDM5A Is Activated and Pathogenic in a Mouse Model of LMNA-Cardiomyopathy.
- 1Center for Cardiovascular Genetics, Institute of Molecular Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
- 2Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- 3Center for Cardiovascular Genetics, Institute of Molecular Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, USA. Electronic address: [email protected].
Abstract
Heart failure is associated with widespread epigenetic remodeling in cardiomyocytes, but the chromatin regulators driving this process remain poorly defined. We identify the histone H3K4 demethylase KDM5A as a key epigenetic mediator of heart failure in a cardiomyocyte-specific lamin A-deficient mouse model. Disease-associated activation of KDM5A leads to redistribution of promoter histone H3 lysine 4 trimethylation and repression of genes regulating sarcomere structure and mitochondrial oxidative metabolism. Genetic deletion of Kdm5a restores histone H3 lysine 4 trimethylation enrichment, reactivates cardiac and metabolic transcriptional programs, improves cardiac function, and prolongs survival. These findings identify KDM5A-mediated chromatin remodeling as a previously unrecognized mechanism of heart failure and highlight KDM5A as a potential therapeutic target.
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BibTeX
@article{deogharia2026histone,
title = {{Histone Demethylase KDM5A Is Activated and Pathogenic in a Mouse Model of LMNA-Cardiomyopathy.}},
author = {Manisha Deogharia and Chitra Lekha Reddy and Ritapa Chaudhuri and Manogna Sai Chirasani and Abhinav K Jain and Leila Rouhi and A J Marian and Priyatansh Gurha},
journal = {JACC. Basic to translational science},
year = {2026},
month = oct,
doi = {10.1016/j.jacbts.2026.101714},
url = {https://europepmc.org/article/MED/42849122},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Histone Demethylase KDM5A Is Activated and Pathogenic in a Mouse Model of LMNA-Cardiomyopathy.
AU - Manisha Deogharia
AU - Chitra Lekha Reddy
AU - Ritapa Chaudhuri
AU - Manogna Sai Chirasani
AU - Abhinav K Jain
AU - Leila Rouhi
AU - A J Marian
AU - Priyatansh Gurha
PY - 2026
DA - 2026/10/08
JO - JACC. Basic to translational science
DO - 10.1016/j.jacbts.2026.101714
UR - https://europepmc.org/article/MED/42849122
AB - Heart failure is associated with widespread epigenetic remodeling in cardiomyocytes, but the chromatin regulators driving this process remain poorly defined. We identify the histone H3K4 demethylase KDM5A as a key epigenetic mediator of heart failure in a cardiomyocyte-specific lamin A-deficient mouse model. Disease-associated activation of KDM5A leads to redistribution of promoter histone H3 lysine 4 trimethylation and repression of genes regulating sarcomere structure and mitochondrial oxidative metabolism. Genetic deletion of Kdm5a restores histone H3 lysine 4 trimethylation enrichment, reactivates cardiac and metabolic transcriptional programs, improves cardiac function, and prolongs survival. These findings identify KDM5A-mediated chromatin remodeling as a previously unrecognized mechanism of heart failure and highlight KDM5A as a potential therapeutic target.
SN - 2452-302X
ER -