Histone lysine methyltransferase 2 (KMT2) proteins form multimeric enzymatic complexes that methylate lysine 4 on histone H3 (H3K4) at transcription regulatory elements in the genome. A strong association of H3K4 methylation with active transcription has led to intense efforts to reveal the functional involvement of KMT2 complexes in transcriptional regulation. A number of biochemical and cellular studies have shown that KMT2 complexes regulate transcription of target genes via H3K4 methylation. However, in many cases, loss of KMT2 complex enzymatic activity fails to fully account for observed transcriptional defects. Accumulating evidence indicates that, in certain contexts, KMT2 complex-mediated transcriptional regulation can occur in an H3K4 methylation-independent manner. Here, we comprehensively review functions of KMT2 complexes in gene expression, focusing on what we currently know about the molecular mechanisms by which the KMT2 complexes regulate transcription. We also discuss how aberrant transcriptional regulation by KMT2 complexes contributes to different human diseases, such as cancer.

中文翻译：

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KMT2组蛋白H3K4甲基转移酶的转录调控。

组蛋白赖氨酸甲基转移酶2（KMT2）蛋白形成多聚酶复合物，在基因组中的转录调控元件处使组蛋白H3（H3K4）上的赖氨酸4甲基化。H3K4甲基化与活跃的转录之间的密切联系已导致付出了巨大的努力，以揭示KMT2复合体在转录调控中的功能性参与。许多生化和细胞研究表明，KMT2复合物通过H3K4甲基化调节靶基因的转录。但是，在许多情况下，KMT2复合酶活性的丧失无法完全解决观察到的转录缺陷。越来越多的证据表明，在某些情况下，KMT2复合物介导的转录调控可能以与H3K4甲基化无关的方式发生。这里，我们全面回顾了KMT2复合物在基因表达中的功能，重点是我们目前对KMT2复合物调节转录的分子机制的了解。我们还讨论了由KMT2复合体引起的异常转录调控如何导致不同的人类疾病，例如癌症。