Histone-3-lysine-4-methylation (H3K4me) is mediated by six different lysine methyltransferases (KMTs). Amongst these enzymes SET domain containing 1b (SETD1B) has been linked to intellectual disability but its role in the adult brain has not been studied yet. Here we show that mice lacking Setd1b from excitatory neurons of the adult forebrain exhibit severe memory impairment. By combining neuron-specific ChIP-seq, RNA-seq and single cell RNA-seq approaches we show that Setd1b controls the expression of neuronal-identity genes with a broad H3K4me3 peak linked to learning and memory processes. Our data furthermore suggest that basal neuronal gene-expression is ensured by other H3K4 KMTs such as Kmt2a and Kmt2b while the additional presence of Setd1b at the single cell level provides transcriptional consistency to the expression of genes important for learning & memory.

中文翻译：

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SETD1B通过细胞类型特异性调节神经元同一性基因来控制认知功能

组蛋白-3-赖氨酸-4-甲基化（H3K4me）由六个不同的赖氨酸甲基转移酶（KMT）介导。在这些酶中，含有1b的SET结构域（SETD1B）与智力障碍有关，但尚未研究其在成年大脑中的作用。在这里，我们显示缺少来自成年前脑兴奋神经元的Setd1b的小鼠表现出严重的记忆障碍。通过结合神经元特异性ChIP-seq，RNA-seq和单细胞RNA-seq方法，我们显示Setd1b控制具有广泛的H3K4me3峰的神经元身份基因的表达，该峰与学习和记忆过程有关。