The histone chaperone Anp32e regulates memory formation, transcription, and dendritic morphology by regulating steady-state H2A.Z binding in neurons.
The histone chaperone Anp32e regulates memory formation, transcription, and dendritic morphology by regulating steady-state H2A.Z binding in neurons.
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DOI：
10.1016/j.celrep.2021.109551
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发表时间：
2021-08-17
期刊：
影响因子：
8.8
通讯作者：
Zovkic IB
中科院分区：
文献类型：
--
作者：
Stefanelli G;Makowski CE;Brimble MA;Hall M;Reda A;Creighton SD;Leonetti AM;McLean TAB;Zakaria JM;Baumbach J;Greer CB;Davidoff AM;Walters BJ;Murphy PJ;Zovkic IB
快速去除组蛋白H2A。来自神经元染色质的Z是学习诱导的基因表达和记忆形成的关键步骤，但学习诱导的H2A的机制。Z的移除是不清楚的。Anp32e最近被鉴定为H2A。去除H2A的z特异性组蛋白伴侣。Z在分裂细胞中来自核小体，但其在非分裂神经元中的作用尚不清楚。此外，先前的研究调查了Anp32e在稳态而非刺激诱导条件下的功能。在这里，我们发现Anp32e调控H2A。稳定状态下神经元中的Z结合，对刺激诱导的H2A影响较小。Z移除。功能上，Anp32e耗竭导致H2A。培养海马神经元转录和树突状树突的z依赖性损伤，以及情境恐惧记忆和转录调节的回忆受损。总之，这些数据表明Anp32e通过阻止H2A来调节行为和形态学结果。染色质中Z的积累而不是通过调节活性介导的H2A。Z动力学。组蛋白变体是神经可塑性和记忆形成的高度动态调节因子。Stefanelli等人表明组蛋白H2A。神经元中的Z受Anp32e调控，Anp32e保留H2A。检查Z绑定。在Anp32e缺乏的情况下，神经元积聚H2A。Z，它们的发育受损，小鼠表现出记忆形成受损。
Rapid removal of histone H2A.Z from neuronal chromatin is a key step in learning-induced gene expression and memory formation, but mechanisms underlying learning-induced H2A.Z removal are unclear. Anp32e was recently identified as an H2A.Z-specific histone chaperone that removes H2A.Z from nucleosomes in dividing cells, but its role in non-dividing neurons is unclear. Moreover, prior studies investigated Anp32e function under steady-state rather than stimulus-induced conditions. Here, we show that Anp32e regulates H2A.Z binding in neurons under steady-state conditions, with lesser impact on stimulus-induced H2A.Z removal. Functionally, Anp32e depletion leads to H2A.Z-dependent impairment in transcription and dendritic arborization in cultured hippocampal neurons, as well as impaired recall of contextual fear memory and transcriptional regulation. Together, these data indicate that Anp32e regulates behavioral and morphological outcomes by preventing H2A.Z accumulation in chromatin rather than by regulating activity-mediated H2A.Z dynamics. Histone variants are highly dynamic regulators of neural plasticity and memory formation. Stefanelli et al. show that histone H2A.Z in neurons is regulated by Anp32e, whereby Anp32e keeps H2A.Z binding in check. In cases of Anp32e deficiency, neurons accumulate H2A.Z, their development is impaired, and mice exhibit impaired memory formation.
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DOI：
10.1073/pnas.1504868112
发表时间：
2015-06-16
影响因子：
11.1
作者：
Gursoy-Yuzugullu, Ozge;Ayrapetov, Marina K.;Price, Brendan D.
通讯作者：
Price, Brendan D.
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
16.6
作者：
Cole L;Kurscheid S;Nekrasov M;Domaschenz R;Vera DL;Dennis JH;Tremethick DJ
通讯作者：
Tremethick DJ
影响因子：
10.5
作者：
Weber CM;Henikoff S
通讯作者：
Henikoff S