Histone-Methyltransferase MLL2 (KMT2B) Is Required for Memory Formation in Mice
Histone-Methyltransferase MLL2 (KMT2B) Is Required for Memory Formation in Mice
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DOI：
10.1523/jneurosci.3356-12.2013
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发表时间：
2013-02-20
影响因子：
5.3
通讯作者：
Fischer, Andre
中科院分区：
文献类型：
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作者：
Kerimoglu, Cemil;Agis-Balboa, Roberto C.;Fischer, Andre
长期记忆的巩固需要差异的基因表达。最近的研究表明，染色质结构的动态变化在调节与记忆形成有关的基因表达程序方面发挥了作用。组蛋白甲基化是染色质可塑性的一个重要调节机制，它是由组蛋白甲基转移酶和组蛋白去甲基酶的抑制活性介导的，然而，组蛋白甲基化的作用还不是很清楚。在这里，我们表明，在成人前脑兴奋性神经元中缺乏组蛋白甲基转移酶髓系/淋巴系或混合系白血病2(MLL2/kmt2b)基因的小鼠表现出海马区依赖的记忆功能受损。与KMT2B在基因激活中的作用一致，DNA微阵列分析显示，缺乏KMT2b的小鼠海马齿状回区域有152个基因下调。下调的可塑性基因显示组蛋白3赖氨酸4二甲基化和三甲基化的特异性缺陷，而组蛋白3赖氨酸4单甲基化不受影响。我们的数据表明，KMT2B介导了海马组蛋白3、赖氨酸4的二甲基化和三甲基化，是记忆形成的关键角色。
The consolidation of long-term memories requires differential gene expression. Recent research has suggested that dynamic changes in chromatin structure play a role in regulating the gene expression program linked to memory formation. The contribution of histone methylation, an important regulatory mechanism of chromatin plasticity that is mediated by the counteracting activity of histone-methyltransferases and histone-demethylases, is, however, not well understood. Here we show that mice lacking the histone-methyltransferase myeloid/lymphoid or mixed-lineage leukemia 2 (mll2/kmt2b) gene in adult forebrain excitatory neurons display impaired hippocampus-dependent memory function. Consistent with the role of KMT2B in gene-activation DNA microarray analysis revealed that 152 genes were downregulated in the hippocampal dentate gyrus region of mice lacking kmt2b. Downregulated plasticity genes showed a specific deficit in histone 3 lysine 4 di-and trimethylation, while histone 3 lysine 4 monomethylation was not affected. Our data demonstrates that KMT2B mediates hippocampal histone 3 lysine 4 di-and trimethylation and is a critical player for memory formation.