Histone modifications affect transcription by changing the chromatin structure. In particular, histone H3 lysine 4 trimethylation (H3K4me3) is one of the most recognized epigenetic marks of active transcription. While many studies have provided evidence of the correlation between H3K4me3 and active transcription, details regarding the mechanism involved remain unclear. The first study on the broad H3K4me3 domain was reported in 2014; subsequently, the function of this domain has been studied in various cell types. In this review, we summarized the recent studies on the role of the broad H3K4me3 domain in transcription, development, memory formation, and several diseases, including cancer and autoimmune diseases. The broadest H3K4me3 domains are associated with increased transcriptional precision of cell‐type‐specific genes related to cell identity and other essential functions. The broad H3K4me3 domain regulates maternal zygotic activation in early mammalian development. In systemic autoimmune diseases, high expression of immune‐responsive genes requires the presence of the broad H3K4me3 domain in the promoter‐proximal regions. Transcriptional repression of tumor‐suppressor genes is associated with the shortening of the broad H3K4me3 domains in cancer cells. Additionally, the broad H3K4me3 domain interacts with the super‐enhancer to regulate cancer‐associated genes. During memory formation, H3K4me3 breadth is regulated in the hippocampus CA1 neurons. Taken together, these findings indicate that H3K4me3 breadth is essential for the regulation of the transcriptional output across multiple cell types.

中文翻译：

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组蛋白H3赖氨酸4三甲基化的广域在转录调控和疾病中。

组蛋白修饰通过改变染色质结构来影响转录。特别是，组蛋白H3赖氨酸4三甲基化（H3K4me3）是最活跃的表观遗传标记之一。尽管许多研究提供了H3K4me3与活性转录之间相关性的证据，但有关机制的细节仍不清楚。2014年首次报道了有关H3K4me3广泛域的研究；随后，已经在各种细胞类型中研究了该结构域的功能。在这篇综述中，我们总结了关于广泛的H3K4me3结构域在转录，发育，记忆形成和几种疾病（包括癌症和自身免疫性疾病）中的作用的最新研究。最广泛的H3K4me3结构域与与细胞身份和其他基本功能有关的细胞类型特异性基因的转录精度提高有关。H3K4me3广泛的域调节哺乳动物早期发育中的母体合子激活。在系统性自身免疫疾病中，免疫应答基因的高表达需要在启动子附近区域存在宽广的H3K4me3结构域。肿瘤抑制基因的转录抑制与癌细胞中广泛的H3K4me3结构域的缩短有关。此外，宽广的H3K4me3结构域与超级增强子相互作用，以调节与癌症相关的基因。在记忆形成过程中，H3K4me3的宽度在海马CA1神经元中受到调节。在一起