New England Biolabs Inc, Ipswich, MA, USA.
Epigenetics. 2009 Aug 16;4(6):383-7. doi: 10.4161/epi.4.6.9450. Epub 2009 Aug 6.
Lysine methylation has emerged as a major posttranslational modification for histones in eukaryotes. Crosstalk between lysine methylation and other posttranslational modifications is crucial for transcriptional gene regulation and epigenetic inheritance. In addition to histones, several other cellular proteins including transcription factors, tumor suppressor and membrane-associated receptors are subject to lysine methylation. SET7/9 plays a prominent role in lysine methylation of histone and non-histone proteins. Recent reports have suggested a new mechanism of epigenetic gene regulation via SET7/9 modulated DNMT1 methylation. In this mechanism, SET7/9 may methylate DNMT1 leading to proteasome mediated protein degradation, and antagonist lysine specific demethylase (LSD), may prevent this degradation by removing the methyl mark. Thus a fine-tuning and balance between cellular SET7/9 and LSD interaction with DNMT1 may be means for epigenetic gene regulation.
赖氨酸甲基化已成为真核生物中组蛋白的一种主要翻译后修饰。赖氨酸甲基化与其他翻译后修饰之间的串扰对于转录基因调控和表观遗传遗传至关重要。除了组蛋白，其他几种细胞蛋白，包括转录因子、肿瘤抑制因子和膜相关受体，都受到赖氨酸甲基化的影响。SET7/9 在组蛋白和非组蛋白蛋白的赖氨酸甲基化中起着重要作用。最近的报道表明，通过 SET7/9 调节的 DNMT1 甲基化，存在一种新的表观遗传基因调控机制。在这种机制中，SET7/9 可能甲基化 DNMT1，导致蛋白酶体介导的蛋白质降解，而拮抗赖氨酸特异性去甲基酶（LSD）可能通过去除甲基标记来防止这种降解。因此，细胞 SET7/9 和 LSD 与 DNMT1 相互作用的精细调节和平衡可能是表观遗传基因调控的一种手段。
