Epigenetic control of neurotransmitter expression in olfactory bulb interneurons.
Epigenetic control of neurotransmitter expression in olfactory bulb interneurons.
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DOI：
10.1016/j.ijdevneu.2012.11.009
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Cave JW
中科院分区：
文献类型：
--
作者：
Banerjee K;Akiba Y;Baker H;Cave JW
确定中枢神经系统中神经元表型多样性发展和维持的分子机制是发育神经生物学的一个基本挑战。绝大多数嗅球（OB）中间神经元是gaba能的，这种神经递质表型通过谷氨酸脱羧酶1 （Gad1）和Gad2的转录或两者的转录在迁移的神经母细胞中被指定。一部分OB中间神经元也共同表达多巴胺，但酪氨酸羟化酶（Th）的转录抑制抑制了多巴胺能表型，直到这些神经元最终分化。在成熟的OB中间神经元中，GABA和多巴胺水平是通过气味诱导的Gad1和Th转录的突触活动依赖调节来调节的。OB中指定和维持gaba能和多巴胺能表型的分子机制尚不清楚。在本报告中，我们回顾了以往的研究并提出了新的发现，这些发现为OB中控制这些神经递质表型表达的表观遗传调控机制的贡献提供了见解。我们发现HDAC酶通过抑制Th转录来抑制迁移神经母细胞中的多巴胺能表型。在成熟的中间神经元中，Th和Gad1的转录水平都是通过Th和Gad1近端启动子上乙酰化组蛋白H3的突触活性依赖性募集来调节的。我们还发现，与Th和Gad1相比，HDAC2对气味诱导的突触活动具有相反的转录反应。这些发现表明，HDAC2在一定程度上介导了成熟OB中间神经元中Th和Gad1近端启动子的活性依赖性染色质重塑。
Defining the molecular mechanisms that underlie development and maintenance of neuronal phenotypic diversity in the CNS is a fundamental challenge in developmental neurobiology. The vast majority of olfactory bulb (OB) interneurons are GABAergic and this neurotransmitter phenotype is specified in migrating neuroblasts by transcription of either or both glutamic acid decarboxylase 1 (Gad1) and Gad2. A subset of OB interneurons also co-express dopamine, but transcriptional repression of tyrosine hydroxylase (Th) suppresses the dopaminergic phenotype until these neurons terminally differentiate. In mature OB interneurons, GABA and dopamine levels are modulated by odorant-induced synaptic activity-dependent regulation of Gad1 and Th transcription. The molecular mechanisms that specify and maintain the GABAergic and dopaminergic phenotypes in the OB are not clearly delineated. In this report, we review previous studies and present novel findings that provide insight into the contribution of epigenetic regulatory mechanisms for controlling expression of these neurotransmitter phenotypes in the OB. We show that HDAC enzymes suppress the dopaminergic phenotype in migrating neuroblasts by repressing Th transcription. In the mature interneurons, both Th and Gad1 transcription levels are modulated by synaptic activity-dependent recruitment of acetylated histone H3 on both the Th and Gad1 proximal promoters. We also show that HDAC2 has the opposite transcriptional response to odorant-induced synaptic activity when compared to Th and Gad1. These findings suggest that HDAC2 mediates, in part, the activity-dependent chromatin remodeling of the Th and Gad1 proximal promoters in mature OB interneurons.
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DOI：
10.1073/pnas.0505394102
发表时间：
2005-08-30
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
7.6
作者：
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影响因子：
64.5
作者：
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影响因子：
5.3
作者：
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通讯作者：
Goetz, Magdalena
影响因子：
4.7
作者：
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通讯作者：
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