A Study for Epigenetic Regulation to Maintain Cardiac Homeostasis

持续的基因激活，如“心脏胎儿基因再激活”，在慢性心力衰竭恶化的机制中起着重要作用。然而，其表达激活的维持机制尚未完全阐明。我们首次发现了衰竭心肌细胞核中异染色质破坏和顺式作用转录因子的矛盾抑制的证据，尽管目标心脏胎儿基因水平升高，表明表观遗传基因调控可能参与了这一现象。此外，我们还建立了新的体内染色质免疫沉淀分析方法，这在心脏组织领域还很难得到应用。表观基因修饰引起的转录敏感性改变被发现在介导心力衰竭的“核记忆”中起着重要作用，为慢性疾病的新的病理理解带来了希望。

Sustained gene activation, such as" cardiac fetal gene reactivation", has an important role in the mechanism underlying exacerbations of chronic heart failure. However, the maintenance mechanism of its expressional activation has not yet been fully elucidated. We first found evidence for heterochromatin disruption in the nucleus of failing cardiomyocytes and paradoxical depression of cis-acting transcription factors, despite elevated levels of target cardiac fetal genes, suggesting that epigenetic gene regulation might be involved in this phenomenon. In addition, we newly developed in vivo chromatin immunoprecipitation assay, which has hardly been applied in the field of cardiac tissue. The proven alteration in transcriptional sensitivity by epigenetic gene modification was found to play a significant role in the" nuclear memory" mediating heart failure, raising the hope for the novel pathological understanding for chronic diseases.