Systematic characterization of the enzyme-substrate network in protein Lysine methylation

尽管Lys甲基化在正常生理和复杂疾病(如癌症和神经疾病)的发病机制中具有重要作用，但除了对组蛋白修饰的作用外，我们对这种翻译后修饰(PTM)知之甚少。我们建议定义赖氨酸甲基转移酶(KMTs)和甲基赖氨酸脱甲基酶(KDMS)的酶-底物网络，以了解Lys甲基化的功能。作为朝着这一雄心勃勃的目标迈出的重要一步，我们将重点描述修改H3K4甲基化的KMT和KDM，这是一种与活跃转录基因相关的组蛋白标记。H3K4甲基化的重要性一方面被大量能够改变标记的KMT(&gt；12)和KDM(&gt；6)所强调，另一方面被相应基因被去除的小鼠的致命性或严重的发育缺陷所突显。

Despite the importance of Lys methylation in normal physiology and the pathogenesis of complex diseases such as cancer and neurological disorder, we know little about this post-translational modification (PTM) beyond its role on histone modification. We propose here to define the enzyme-substrate network of lysine methyltransferases (KMTs) and methyllyinse demethylases (KDMs) in order to understand the function of Lys methylation. As an important step towards this ambitious goal, we will focus on characterizing the KMTs and KDMs that modify H3K4 methylation, a histone mark that is associated with actively transcribed genes. The importance of H3K4 methylation is underscored, on the one hand, by the large number of KMTs (>12) and KDMs (>6) that are capable of modifying the mark, and, on the other, by the lethality or severe developmental defects in mice in which the corresponding genes are ablated.