Mature cardiomyocytes recall their progenitor experience via polycomb repressive complex 2.
Mature cardiomyocytes recall their progenitor experience via polycomb repressive complex 2.
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DOI：
10.1161/res.0b013e3182635cbf
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发表时间：
2012-07
影响因子：
20.1
通讯作者：
Aibin He;W. Pu
中科院分区：
文献类型：
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作者：
Aibin He;W. Pu
Ezh 2对心脏祖细胞基因表达的表观遗传抑制是出生后心脏稳态所必需的。2012;44：343-347.多梳抑制复合物2（PRC 2）沉积抑制性表观遗传标记，使不适当的基因表达程序沉默。Delgado-Olguin等人1的最新工作结合其他实验室的研究2 -4表明，心脏祖细胞中的PRC 2活性影响成熟心肌细胞的生长和基因表达。这些研究说明了表观遗传机制的力量，以保留有关心脏发育史的信息，并将其用于影响成熟的心脏功能。妊娠期和出生后心脏所经历的生理和病理生理应激对心脏功能有长期影响。心如何记住它过去的经历？Delgado-Olguin等人1的最新研究以及我们小组2，3和另一个实验室4同时发表的研究强调了表观遗传机制在塑造心肌功能中的关键作用，并提供了一种可能支持心脏记忆分子实现的分子机制（图）。图.心脏祖细胞中EZH 2介导的基因沉默是成年心肌细胞生长和功能正常调节所必需的。EZH 2在心脏祖细胞（CPC）中沉积抑制性H3 K27 me 3表观遗传标记，建立Six 1沉默所需的染色质景观。CPC中的EZH 2消融阻断了这些标记的初始沉积，即使在EZH 2活性不存在的后期阶段也可以解抑制Six 1。SIX 1激活异位骨骼肌基因表达，导致成人心肌细胞肥大和纤维化。然而，SIX 1单独上调不足以引起EZH 2突变体中所见的表型。例如，Ink 4a/B细胞周期抑制剂的上调可能导致心肌发育不全。在目前的说法中，表观遗传学是指在细胞分裂或世代之间活跃的机制，这些机制导致可遗传的基因表达变化，而不涉及DNA序列的变化。表观遗传调控机制涉及对DNA（如DNA甲基化）或组蛋白的修饰，或核小体周围DNA的高阶包装。这些...
### Epigenetic Repression of Cardiac Progenitor Gene Expression by Ezh2 is Required for Postnatal Cardiac Homeostasis Delgado-Olguin et al Nat Genet . 2012;44:343–347. Polycomb repressive complex 2 (PRC2) deposits repressive epigenetic marks that silence inappropriate gene expression programs. Recent work from Delgado-Olguin et al1 in conjunction with studies from other laboratories2–4 show that PRC2 activity in cardiac progenitors influences growth and gene expression of mature cardiomyocytes. These studies illustrate the power of epigenetic mechanisms to retain information about the heart's developmental history and deploy it to influence mature heart function. Physiological and pathophysiological stresses experienced by the heart during gestation and postnatal life have longstanding effects on heart function. How does the heart remember its past experiences? Recent work by Delgado-Olguin et al1 and concurrently published work from our group2,3 and another laboratory4 highlight the key role of epigenetic mechanisms in shaping myocardial function and provide a molecular mechanism that likely underpins molecular implementation of cardiac memory (Figure). Figure. EZH2-mediated gene silencing in cardiac progenitors is required for normal regulation of adult cardiomyocyte growth and function. EZH2 deposits repressive H3K27me3 epigenetic marks in cardiac progenitor cells (CPCs), establishing a chromatin landscape that is required for silencing of Six1 . EZH2 ablation in CPCs blocks initial deposition of these marks, derepressing Six1 even in later stages when EZH2 activity is dispensible. SIX1 activates ectopic skeletal muscle gene expression, which contributes to adult cardiomyocyte hypertrophy and fibrosis. However, SIX1 upregulation alone is not sufficient to cause the phenotype seen in EZH2 mutants. For example, upregulation of the Ink4a/b cell cycle inhibitors likely contributes to myocardial hypoplasia. In current parlance, epigenetics refers to mechanisms active over rounds of cell division or between generations that lead to heritable gene expression changes without involving changes to the DNA sequence. Epigenetic regulatory mechanisms involve modifications to DNA (eg, DNA methylation) or histones, or higher-order packaging of DNA around nucleosomes. These …