Zhu Jun-Yi, van de Leemput Joyce, Han Zhe
Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Cardiovasc Dev Dis. 2023 Jul 18;10(7):305. doi: 10.3390/jcdd10070305.
Epigenetic marks regulate the transcriptomic landscape by facilitating the structural packing and unwinding of the genome, which is tightly folded inside the nucleus. Lysine-specific histone methylation is one such mark. It plays crucial roles during development, including in cell fate decisions, in tissue patterning, and in regulating cellular metabolic processes. It has also been associated with varying human developmental disorders. Heart disease has been linked to deregulated histone lysine methylation, and lysine-specific methyltransferases (KMTs) are overrepresented, i.e., more numerous than expected by chance, among the genes with variants associated with congenital heart disease. This review outlines the available evidence to support a role for individual KMTs in heart development and/or disease, including genetic associations in patients and supporting cell culture and animal model studies. It concludes with new advances in the field and new opportunities for treatment.
表观遗传标记通过促进基因组的结构包装和解旋来调节转录组景观，基因组在细胞核内紧密折叠。赖氨酸特异性组蛋白甲基化就是这样一种标记。它在发育过程中发挥着关键作用，包括在细胞命运决定、组织模式形成以及调节细胞代谢过程中。它还与多种人类发育障碍有关。心脏病与组蛋白赖氨酸甲基化失调有关，在与先天性心脏病相关的变异基因中，赖氨酸特异性甲基转移酶（KMTs）的数量过多，即比预期的偶然数量更多。本综述概述了支持个体KMTs在心脏发育和/或疾病中作用的现有证据，包括患者的遗传关联以及支持性的细胞培养和动物模型研究。最后介绍了该领域的新进展和新的治疗机会。
