γ-氨基丁酸受体基因的系统性调控网络

发布时间：2018-05-10 12:03

本文选题：分子生物学 + γ-氨基丁酸受体　；参考：《深圳大学学报(理工版)》2015年02期

【摘要】：提出一种多学科交叉结合的策略,试图初步获得系统性调控γ-氨基丁酸(gamma-aminobutyric acid,GABA)受体基因的转录因子线索.利用基于功能基因组学方法的DNA元件百科全书计划已发表的数据,系统性地获得GABA受体基因的开放染色质序列,并以此作为固相化探针,捕获与其特异性相互作用的蛋白质分子,并利用质谱分析鉴定蛋白.结果发现,对不同脑区获得的核蛋白,探针都能捕获到同样的特异性条带,然而,作为对照的天门冬氨酸(N-methyl-D-aspartate,NMDA)受体基因相关的开放染色质探针,在不同脑区中并未检获上述特异信号,说明结合蛋白是特异的.质谱分析表明,与GABA受体基因相关的开放染色质特异相互作用的蛋白是核膜血影重复蛋白-1(nuclear envelop spectrin repeatprotein-1,Nesprin-1),又称synaptic nuclear envelope-1(SYNE-1).进一步的调控网络生物信息学分析表明,Nesprin-1可能与MAFA、IRX2、BCL6、CEBPA以及RP58等转录因子形成复合物,并与GABA受体基因GABRA5、GABRA6、GABBR1和GABBR2等共表达.表明GABA受体基因在不同脑区是通过相同的转录调控机制进行表达的,Nesprin-1可能与MAFA、IRX2、BCL6、CEBPA以及RP58等转录因子形成复合物进而调控GABA受体基因表达,该特异的转录因子调控网络有望用于诱导多能干细胞或是前体细胞直接分化为GABA能神经元.
[Abstract]:A multidisciplinary cross-binding strategy was proposed to obtain the transcriptional factor clues for systematic regulation of gamma-aminobutyric GABA receptor gene. Using published data from the Encyclopedia of DNA components based on functional Genomics approach, the open chromatin sequence of GABA receptor gene was systematically obtained and used as a solid-phase probe. Protein molecules interacting with them were captured and identified by mass spectrometry. The results showed that the probes could capture the same specific bands for nuclear proteins obtained from different brain regions. However, the open chromatin probes associated with the gene of N-methyl-D-aspartate NMDA-receptor of aspartate were used as controls. These specific signals were not seized in different brain regions, indicating that the binding protein was specific. Mass spectrometric analysis showed that the open chromatin specific interaction protein associated with GABA receptor gene was nuclear envelop spectrin repeat protein -1 and nuclear envelop spectrin repeat protein-1, also known as synaptic nuclear envelope 1 and SYNE-1. Further bioinformatics analysis of regulatory networks suggested that Nesprin-1 may form complexes with transcription factors such as MAFAAIRX2BCL6, CEBPA and RP58, and co-express with GABA receptor gene GABRA5, GABRA6GABBR1 and GABBR2. It is suggested that the expression of GABA receptor gene in different brain regions is through the same transcriptional regulation mechanism. Nesprin-1 may be a complex of transcription factors, such as MAFA-IRX2BCL6, CEBPA and RP58, and then regulate the expression of GABA receptor gene. This specific transcription factor regulatory network is expected to be used to induce pluripotent stem cells or progenitor cells to differentiate directly into GABA neurons.
【作者单位】：中山大学附属第六医院神经科;深圳大学光电工程学院;
【基金】：广东省医学科学技术研究基金资助项目(A2012211) 广州市天河区科技计划重点资助项目(201404KW028)~~
【分类号】：R3416

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