Regulation of chromatin states and gene expression during HSN neuronal maturation is mediated by EOR-1/PLZF, MAU-2/cohesin loader, and SWI/SNF complex.

Regulation of chromatin states and gene expression during HSN neuronal maturation is mediated by EOR-1/PLZF, MAU-2/cohesin loader, and SWI/SNF complex.
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DOI:
10.1038/s41598-018-26149-2
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发表时间:
2018-05-21
期刊:
影响因子:
4.6
通讯作者:
Doi M
Doi M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shinkai Y;Kuramochi M;Doi M

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新生神经元通过与表观遗传变化一致的特定基因表达程序的及时诱导,通过不同的顺序步骤成熟。然而,在神经元成熟过程中,在单细胞分辨率下研究基因表达与表观遗传变化之间的关系一直是困难的。在这项研究中,我们研究了雌雄同体特异性神经元(HSNs)的成熟。elegans,它提供了染色质动力学,基因表达和神经元成熟程度之间的联系,在单细胞分辨率。我们的研究结果表明,染色质组成的启动子区域的几个基因的神经元终末成熟的调制在早期发育阶段,是依赖于转录因子EOR-1/PLZF和粘附装载MAU-2/MAU 2的功能。SWI/SNF染色质重塑复合物的组分也是终末成熟基因正确表达所必需的。上位性分析表明eor-1与mau-2和swsn-1在相同的遗传途径中调节HSNs的成熟。总的来说,我们的研究提供了一种分析神经元成熟的新方法,并提出由EOR-1、MAU-2和SWI/SNF复合物介导的预定义表观遗传修饰对于神经元终末成熟中未来基因表达程序的准备非常重要。
Newborn neurons mature by distinct and sequential steps through the timely induction of specific gene expression programs in concert with epigenetic changes. However, it has been difficult to investigate the relationship between gene expression and epigenetic changes at a single-cell resolution during neuronal maturation. In this study, we investigated the maturation of hermaphrodite-specific neurons (HSNs) in C. elegans, which provided the link between chromatin dynamics, gene expression, and the degree of neuronal maturation at a single-cell resolution. Our results demonstrated that chromatin composition in the promoter region of several genes acting for neuronal terminal maturation was modulated at an early developmental stage, and is dependent on the function of the transcription factor EOR-1/PLZF and the cohesin loader MAU-2/MAU2. Components of the SWI/SNF chromatin remodeling complex were also required for the proper expression of terminal maturation genes. Epistasis analyses suggested that eor-1 functions with mau-2 and swsn-1 in the same genetic pathway to regulate the maturation of HSNs. Collectively, our study provides a novel approach to analyze neuronal maturation and proposes that predefined epigenetic modifications, mediated by EOR-1, MAU-2, and the SWI/SNF complex, are important for the preparation of future gene expression programs in neuronal terminal maturation.
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