Systemic depletion of histone macroH2A1.1 boosts hippocampal synaptic plasticity and social behavior in mice
Systemic depletion of histone macroH2A1.1 boosts hippocampal synaptic plasticity and social behavior in mice
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DOI：
10.1096/fj.202100569r
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发表时间：
2021-08-01
期刊：
影响因子：
4.8
通讯作者：
Vinciguerra, Manlio
中科院分区：
文献类型：
--
作者：
Chiodi, Valentina;Domenici, Maria Rosaria;Vinciguerra, Manlio
几个大脑区域的基因表达和表观遗传过程调节生理过程，如认知功能和社会行为。MacroH2A1.1是组蛋白H2 A的普遍存在的变体，其调节各种器官中的细胞干细胞性和分化。macroH2A1.1是否在情绪行为中具有调节作用尚不清楚。在这里，我们采用macroH2A1.1基因敲除（（-/-））小鼠进行全面的电池的行为测试，并评估海马突触可塑性（长时程增强）伴随着整个海马RNA测序。MacroH2A1.1（-/-）小鼠表现出社交能力和主动压力应对行为的惊人增强，分别反映在社交活动测试中的社交行为增加和强迫游泳测试中的移动时间增加。它们还表现出增加的海马突触可塑性，伴随着显着的神经传递转录网络的变化。这些结果表明，组蛋白macroH2A1.1的系统性耗竭支持海马功能和社会行为所必需的表观遗传控制。
Gene expression and epigenetic processes in several brain regions regulate physiological processes such as cognitive functions and social behavior. MacroH2A1.1 is a ubiquitous variant of histone H2A that regulates cell stemness and differentiation in various organs. Whether macroH2A1.1 has a modulatory role in emotional behavior is unknown. Here, we employed macroH2A1.1 knock-out ((-/-)) mice to perform a comprehensive battery of behavioral tests, and an assessment of hippocampal synaptic plasticity (long-term potentiation) accompanied by whole hippocampus RNA sequencing. MacroH2A1.1(-/-) mice exhibit a stunningly enhancement both of sociability and of active stress-coping behavior, reflected by the increased social behavior in social activity tests and higher mobility time in the forced swim test, respectively. They also display an increased hippocampal synaptic plasticity, accompanied by significant neurotransmission transcriptional networks changes. These results suggest that systemic depletion of histone macroH2A1.1 supports an epigenetic control necessary for hippocampal function and social behavior.