Epigenetic stability in the adult mouse cortex under conditions of pharmacologically induced histone acetylation.
Epigenetic stability in the adult mouse cortex under conditions of pharmacologically induced histone acetylation.
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DOI：
10.1007/s00429-015-1138-0
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发表时间：
2016-11
影响因子：
3.1
通讯作者：
Rakic P
中科院分区：
文献类型：
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作者：
Benoit J;Ayoub A;Rakic P
组蛋白乙酰化被认为是影响大脑发育、突触可塑性以及学习和记忆的主要表观遗传过程。由于组蛋白乙酰化的长期修饰，导致可塑性的转录效应物和形态变化尚不完全清楚。为此，我们使用曲古抑素A在成年(6个月大)小鼠中从药物上抑制了组蛋白去乙酰化，并发现乙酰化组蛋白标记H3Lys9、H3Lys14和H4Lys12的水平显著增加。对不同大脑区域的高分辨率转录组分析发现，治疗组和对照组动物之间的基因表达几乎没有差异，这些差异都与可塑性无关。相反，在组蛋白乙酰化增加后，我们检测到大量新的转录活性区域，这些区域对应于长的非编码RNA(LncRNAs)。我们还惊讶地发现，使用长期活体双光子成像技术，在视觉皮质的第1层和第2/3层中，树突棘的可塑性没有显著变化。我们的结果表明，慢性药物诱导的组蛋白乙酰化可以从基因表达中分离出来，相反，可能通过不同的lncRNAs产生而发挥转录后效应。
Histone acetylation is considered a major epigenetic process that affects brain development and synaptic plasticity, as well as learning and memory. The transcriptional effectors and morphological changes responsible for plasticity as a result of long-term modifications to histone acetylation are not fully understood. To this end, we pharmacologically inhibited histone deacetylation using Trichostatin A in adult (6-month-old) mice and found significant increases in the levels of the acetylated histone marks H3Lys9, H3Lys14 and H4Lys12. High-resolution transcriptome analysis of diverse brain regions uncovered few differences in gene expression between treated and control animals, none of which were plasticity related. Instead, after increased histone acetylation, we detected a large number of novel transcriptionally active regions, which correspond to long non-coding RNAs (lncRNAs). We also surprisingly found no significant changes in dendritic spine plasticity in layers 1 and 2/3 of the visual cortex using long-term in vivo two-photon imaging. Our results indicate that chronic pharmacologically induced histone acetylation can be decoupled from gene expression and instead, may potentially exert a post-transcriptional effect through the differential production of lncRNAs.