Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis  

Oleh:

Delgado-Olguin, Paul ; Yu, Huang ; Xue, Li

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 44 no. 03 (Mar. 2012), page 343–347.

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K.2012.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Adult-onset diseases can be associated with in utero events, but mechanisms for this remain unknown1, 2. The Polycomb histone methyltransferase Ezh2 stabilizes transcription by depositing repressive marks during development that persist into adulthood3, 4, 5, 6, 7, 8, 9, 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 differentiation10. 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.

Opini Anda

Klik untuk menuliskan opini Anda tentang koleksi ini!

Kembali