#Lin heart to heart 2 series#
Since the chromatin landscape is established through a series of steps, each contingent upon normal completion of prior steps, transient disruption, through environmental mishaps or genetic mutations, might be anticipated to break the normal sequence and irreversibly impact organ development and function.
This transcriptional regulation depends upon the interplay of an array of epigenetic regulators, which shape the epigenetic landscape by repositioning nucleosomes and depositing covalent modifications on histones. Normal developmental maturation of organ function requires precise transcriptional regulation of gene expression. Our results further illustrate that organ dysfunction due to epigenetic dysregulation can be corrected by epigenetic rewiring. Our results uncovered a non-canonical, H3K27me3-independent EED repressive mechanism that is essential for normal heart function. HDAC overexpression normalized Eed CKO heart function and expression of derepressed genes. EED interacted with histone deacetylases (HDACs) and enhanced their catalytic activity. Rather, the activating histone mark H3K27ac increased. Surprisingly, gene upregulation in Eed CKO was not coupled with loss of H3K27me3. EED (embryonic ectoderm development) inactivation in the postnatal heart (Eed CKO) caused lethal dilated cardiomyopathy. Here, we studied PRC2 function in postnatal mouse cardiomyocytes, where the paucity of cell division obviates bulk H3K27me3 rewriting after each cell cycle. However, it is uncertain whether PRC2 writing of H3K27me3 is mechanistically required for gene silencing. In proliferating cells, where most Polycomb repressive complex 2 (PRC2) studies have been performed, gene repression is associated with PRC2 trimethylation of H3K27 (H3K27me3).
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