The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis
Open accessAbstract
Adult-onset diseases can be associated with in utero events, but mechanisms for this remain unknown. The Polycomb histone methyltransferase Ezh2 stabilizes transcription by depositing repressive marks during development that persist into adulthood, but its function in postnatal organ homeostasis is unknown. We show that Ezh2 stabilizes cardiac gene expression and prevents cardiac pathology by repressing the homeodomain transcription factor gene Six1, which functions in cardiac progenitor cells but is stably silenced upon cardiac differentiation. Deletion of Ezh2 in cardiac progenitors caused postnatal myocardial pathology and destabilized cardiac gene expression with activation of Six1-dependent skeletal muscle genes. Six1 induced cardiomyocyte hypertrophy and skeletal muscle gene expression. Furthermore, genetically reducing Six1 levels rescued the pathology of Ezh2-deficient hearts. Thus, Ezh2-mediated repression of Six1 in differentiating cardiac progenitors is essential for stable gene expression and homeostasis in the postnatal heart. Our results suggest that epigenetic dysregulation in embryonic progenitor cells is a predisposing factor for adult disease and dysregulated stress responses.
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Cites
The Polycomb complex PRC2 and its mark in life
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Ezh1 and Ezh2 Maintain Repressive Chromatin through Different Mechanisms
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Chromatin structure and the inheritance of epigenetic information
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Self-citationEpigenetic mechanisms that underpin metabolic and cardiovascular diseases
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Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement
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Metadata
- Authors
- Delgado-Olguín, P., Huang, Y., Li, X., Christodoulou, D., Seidman, C. E., Seidman, J. G., Tarakhovsky, A., & Bruneau, B. G.
- Venue
- Nature Genetics
- Published
- 2012-01-22
- Volume
- 44
- Issue
- 3
- Pages
- 343-347
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2012252035
- Cited by
- 259
- References
- 24
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- green
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