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Curr Opin Chem Biol. 2013 Jun;17(3):369-78. doi: 10.1016/j.cbpa.2013.03.035. Epub 2013 Apr 23.
Protein and DNA methylation have emerged as critical mechanisms for the control of regulated gene transcription. In humans, the addition, recognition and removal of methyl groups are orchestrated by at least 344 proteins that we collectively refer to as the 'methylome'. The large size of the methylome likely reflects the importance of precise control over this small covalent modification. An increasing number of reports implicating the misregulation of methylation in disease make the proteins governing this modification attractive target for small molecule drug discovery. In light of the emerging opportunities for the development of therapeutics that modulate methylation-dependent pathways, this review examines the protein families that constitute the methylome, with emphasis on the methylation of arginine and lysine residues of proteins. Genetic aberrations that give rise to disease are highlighted, in addition to recent proof-of-concept successes in the development of small molecule modulators of methylome constituents.
蛋白质和 DNA 甲基化已成为调控基因转录的关键机制。在人类中，甲基的添加、识别和去除由至少 344 种蛋白质来协调，我们统称这些蛋白质为“甲基组”。甲基组的庞大可能反映了对这种小的共价修饰进行精确控制的重要性。越来越多的报告表明，甲基化的失调与疾病有关，这使得调控这种修饰的蛋白质成为小分子药物发现的有吸引力的靶标。鉴于调节依赖于甲基化的途径的治疗方法的发展机会不断涌现，本综述考察了构成甲基组的蛋白质家族，重点是蛋白质精氨酸和赖氨酸残基的甲基化。除了最近在小分子甲基组成分调节剂的开发方面取得的概念验证成功之外，本文还强调了导致疾病的遗传异常。
