Studying a propionic acidaemia mouse model reveals epigenetic mechanisms in the heart

We show how a build-up of propionyl-CoA in a mouse model of propionic acidaemia produces histone modifications in the heart. The transcriptional responses included genes implicated in contractile dysfunction. Notably, female mice are more severely affected, owing to a protective effect of β-alanine in males, a therapeutically important finding.

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Fig. 1: Sex-dependent changes in histone modifications in the hypomorphic mouse model of PA.

References

Richard, E., Pérez, B., Pérez-Cerdá, C. & Desviat, L. R. Understanding molecular mechanisms in propionic acidemia and investigated therapeutic strategies. Expert Opin. Orphan Drugs 3, 1427–1438 (2015). This review presents an overview of propionic acidemia.

Article
CAS

Google Scholar
Kebede, A. F. et al. Histone propionylation is a mark of active chromatin. Nat. Struct. Mol. Biol. 24, 1048–1056 (2017). This paper reports histone propionylation in vivo.

Article
CAS
PubMed

Google Scholar
He, W., Wang, Y., Xie, E. J., Barry, M. A. & Zhang, G.-F. Metabolic perturbations mediated by propionyl-CoA accumulation in organs of mouse model of propionic acidemia. Mol. Gen. Metab. 134, 257–266 (2021). This review discusses the metabolic changes in propionic acidemia.

Article
CAS

Google Scholar
Guenzel, A. J. et al. Generation of a hypomorphic model of propionic acidemia amenable to gene therapy testing. Mol. Ther. 21, 1316–1323 (2013). This paper introduces the hypomorphic mouse model of PA.

Article
CAS
PubMed
PubMed Central

Google Scholar
Gillette, T. G. & Hill, J. A. Readers, writers, and erasers: chromatin as the whiteboard of heart disease. Circ. Res. 116, 1245–1253 (2015). The review discusses the role of changes in chromatin structure in cardiac disease.

Article
CAS
PubMed
PubMed Central

Google Scholar

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This is a summary of: Park, K. C. et al. Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation. Nat. Cardiovas. Res. https://doi.org/10.1038/s44161-023-00365-0 (2023).

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Studying a propionic acidaemia mouse model reveals epigenetic mechanisms in the heart.
Nat Cardiovasc Res (2023). https://doi.org/10.1038/s44161-023-00371-2

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Published: 29 November 2023
DOI: https://doi.org/10.1038/s44161-023-00371-2

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