| 1 | 摩尔。精神病学2006年12月11日：1126-38 |
|---|---|
| PMID | 16924267 |
| Title | 涉及BRD1的证据与精神分裂症和双相情感障碍有关脑发育和易感性。 |
| 抽象的 | Linkage studies suggest that chromosome 22q12-13 may contain one or more shared susceptibility genes forschizophrenia(SZ) and bipolar affective disorder (BPD). In a Faeroese sample, we previously reported association between microsatellite markers located at 22q13.31-qtel and both disorders. The present study reports an association analysis across five genes (including 14 single nucleotide and two microsatellite polymorphisms) in this interval using a case-control sample of 162 BPD, 103 SZ patients and 200 controls. The bromodomain-containing 1 gene (BRD1), which encodes a putative regulator of transcription showed association with both disorders with minimal P-values of 0.0046 and 0.00001 for single marker and overall haplotype analysis, respectively. A specificBRD12-marker 'risk' haplotype showed a frequency of approximately 10% in the combined case group versus approximately 1% in controls (P-value 2.8 x 10(-7)). Expression analysis ofBRD1mRNA revealed widespread expression in mammalian brain tissue, which was substantiated by immunohistochemical detection ofBRD1protein in the nucleus, perikaryal cytosol and proximal dendrites of the neurons in the adult rat, rabbit and human CNS. Quantitative mRNA analysis in developing fetal pig brain revealed spatiotemporal differences with high expression at early embryonic stages, with intense nuclear and cytosolar immunohistochemical staining of the neuroepithelial layer and early neuroblasts, whilst more mature neurons at later embryonic stages had less nuclear staining. The results implicateBRD1with SZ and BPD susceptibility and provide evidence that suggests a role forBRD1在神经发育中。 |
| SCZ Keywords | schizophrenia |
| 2 | Brain Struct Funct 2009 Dec 214: 37-47 |
| PMID | 19763615 |
| Title | BRD1的进一步免疫组织化学表征是精神分裂症和双相情感障碍的新易感基因。 |
| 抽象的 | 我们最近表明该基因BRD1is associated withschizophreniaand bipolar affective disorder and that theBRD1protein (BRD1) which is expressed in neurons may occur in a short and a long variant. The aim of the study was to generate polyclonal antibodies against newBRD1epitopes enabling discrimination between the long and shortBRD1变体，并阐明BRD1distribution in several human tissues, including the CNS. Polyclonal rabbit antibodies were raised against three differentBRD1表位。一个（67）特定于长期BRD1variant, whereas the two others (63/64 and 65/66) like the original monoclonal mouse antibody (K22) were predicted to stain both variants. Immunohistochemical staining procedures were subsequently performed on paraffin-embedded human cerebral cortex and microarray slides containing 30 different human tissues. Western blotting confirmed the predicted specificity of the developed antibodies. K22, 63/64 and 65/66 displayed a similar neuronal staining pattern characterized by a distinct but weak nuclear staining, while the surrounding cytoplasm and proximal dendrites were more intensely stained. Interestingly, staining with 67 generated in contrast primarily an intense nuclear staining. The new antibodies resulted, furthermore, in a prominent neuroglial reaction characterized by staining of cell bodies, nuclei and glial processes. The tissue microarray analysis revealed thatBRD1被广泛分布在人体组织中。但是，特定的表达谱，例如，核和/或细胞质染色的程度似乎是高度依赖的。这些结果表明BRD1在细胞中，强调两者BRD1variants may play different roles in the etiology of psychiatric disease. |
| SCZ Keywords | schizophrenia |
| 3 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Mar 153B: 582-91 |
| PMID | 19693800 |
| Title | BRD1与精神分裂症与双相情感障碍之间的联系。 |
| 抽象的 | A recent study published by our group implicated the bromodomain containing protein 1 (BRD1) gene located at chromosome 22q13.33 withschizophrenia（SZ）和双相情感障碍（BPD）敏感性，并提供了证据，表明可能作用BRD1在神经发育中。本研究报告了对BRD1and the neighboring gene ZBED4 using a Caucasian case-control sample from Denmark and England (UK/DK sample: 490 patients with BPD, 527 patients with SZ, and 601 control individuals), and genotypes obtained from a BPD genome wide association (GWA) study of an overlapping English sample comprising 506 patients with BPD and 510 control individuals (UCL sample). In the UK/DK sample we genotyped 11 SNPs in theBRD1区域，其中六个显示与SZ（最小单个标记p值为0.0014），其中包括两个先前在苏格兰人群中显示关联的SNP [Severinsen等。（2006）;摩尔精神病学11（12）：1126-1138]。单倍型分析揭示了特定的风险和保护性单倍型，最小的P值为0.0027。11个SNP中没有一个与BPD结合。但是，分析七个BRD1SNPs obtained from the BPD GWA study, positive associations with BPD was observed with all markers (minimal P-value of 0.0014). The associations reported add further support for the implication ofBRD1具有SZ和BPD敏感性。 |
| SCZ Keywords | schizophrenia |
| 4 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Apr 153B: 786-91 |
| PMID | 19908236 |
| Title | 协会bromodomain-containing 1基因的研究with schizophrenia in Japanese population. |
| 抽象的 | 染色体22q13区域已与schizophrenia在几个链接研究中。因此，该基因座中的基因是有希望的遗传和生物学候选基因schizophrenia如果它们在大脑中表达或预测在大脑发育中起作用。最近的一项研究报道说，含溴脱域的1个基因（BRD1), located in 22q13, showed an association withschizophreniain a Scottish population. Except for being a putative regulator of transcription, the precise function ofBRD1不清楚;但是，表达分析BRD1mRNA revealed widespread expression in mammalian brains. In our study, we explored the association ofBRD1withschizophrenia在日本人口中（626例和770个对照）。在此关联分析中，我们首先检查了10个直接基因分型单核苷酸多态性（SNP）和20个估算的SNP。第二，我们比较了BRD1病例和对照之间的mRNA水平使用源自29例和30个对照的淋巴母细胞系（LCL）。尽管以前与之相关的SNP（RS138880）schizophreniashowed the same trend in the Japanese population, no significant association was detected betweenBRD1andschizophrenia在我们的研究中。同样，没有显着差异BRD1检测到LCL中的mRNA水平。综上所述，我们无法强烈证明BRD1gene account for a substantial proportion of the genetic risk forschizophrenia在日本人口中。 |
| SCZ Keywords | schizophrenia |
| 5 | Neurosci。Lett。2012年5月516日：110-3 |
| PMID | 22675730 |
| Title | Electroconvulsive seizures regulates the Brd1 gene in the frontal cortex and hippocampus of the adult rat. |
| 抽象的 | Depressive disorders represent a significant health concern as they are associated with high social and physical dysfunction and increased risk for suicide. Electroconvulsive therapy (ECT) is the most effective treatment for patients with drug-resistant severe depressive disorders. However, the underlying biological mechanisms of ECT are not well characterized. In particular, the regulation of transcription factors upon ECT has only just started to be unveiled. Theschizophrenia和二极性疾病相关的溴结构域包含1（BRD1）基因对于组蛋白H3K14的乙酰化很重要，并且在正常的胚胎发育和生存中具有关键作用。在这项研究中，我们测量了BRD1在急性和重复的电弹力癫痫发作（EC）的雄性Sprague-Dawley大鼠海马和额叶皮层中的mRNA在10天内。我们发现一般表达的增加BRD1与假手术相比，重复ECS后海马中的mRNA（f = 8.108，p = 0.003）。此外，我们提供了证据，表明表达的降低BRD1mRNA variant comprising an extended version of exon 7 (BRD1与假手术相比，重复ECS后额叶皮质中的-l）（f = 6.225，p = 0.023）。这些发现表明对BRD1基因是对EC的生物学反应的一部分，在不同的大脑区域中，剪接变体被诱导。 |
| SCZ Keywords | schizophrenia |
| 6 | Eur Neuropsychopharmacol 2012年9月22日：651-6 |
| PMID | 22341945 |
| Title | The Schizophrenia and Bipolar Disorder associated BRD1 gene is regulated upon chronic restraint stress. |
| 抽象的 | 最近的遗传证据暗示了含有1个基因的溴结构域（BRD1）大脑发育和易感性schizophreniaand Bipolar Disorder. TheBRD1蛋白质对于组蛋白H3K14的乙酰化至关重要，是大脑发育和成熟中枢神经系统过程中转录的推定调节剂。但是，例如，关于调节的问题仍然有待澄清BRD1环境干预措施的基因。大鼠中的慢性约束应力（CRS）代表了一种环境方法，用于诱导海马和前额叶皮层的形态和功能变化。为了研究大鼠的表达是否BRD1gene may be regulated during such conditions,BRD1mRNA and protein levels in hippocampus and prefrontal cortex extracts from rats subjected to either 1/2 or 6h of CRS per day for 21days were measured. We found a significant 2-fold up-regulation of long exon 7 splice variants of theBRD1基因（BRD1与对照组相比，两组CRS大鼠的海马中的-l）。同时，我们发现了类似的上调BRD1蛋白质。在前额叶皮层中，我们发现没有显着差异BRD1mRNA或蛋白质水平。由于选择性组蛋白脱乙酰基酶（HDAC）抑制剂不仅保留了组蛋白H3K14的应激诱导的高乙酰化，而且还具有海马依赖性抗抑郁药样活性，我们建议BRD1by its intrinsic acetylation activity towards histone H3K14 is a player in the regulatory processes underlying adaptation to stress in the mature CNS. |
| SCZ Keywords | schizophrenia |
| 7 | Genome Med 2016 -1 8：53 |
| PMID | 27142060 |
| Title | Identification of the BRD1 interaction network and its impact on mental disorder risk. |
| 抽象的 | The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development, and susceptibility toschizophrenia和躁郁症。促进对BRD1及其在精神障碍中的作用，我们表征了蛋白质和染色质的相互作用BRD1isoforms,BRD1-沙BRD1-l。 Stable human cell lines expressing epitope taggedBRD1-沙BRD1发现系统fo - l生成和使用r identifying protein and chromatin interactions. Protein-protein interactions were identified using co-immunoprecipitation followed by mass spectrometry and chromatin interactions were identified using chromatin immunoprecipitation followed by next generation sequencing. Gene expression profiles and differentially expressed genes were identified after upregulating and downregulatingBRD1expression using microarrays. The presented functional molecular data were integrated with human genomic and transcriptomic data using available GWAS, exome-sequencing datasets as well as spatiotemporal transcriptomic datasets from the human brain. We present several novel protein interactions ofBRD1, including isoform-specific interactions as well as proteins previously implicated with mental disorders. ByBRD1-沙BRD1-L chromatin immunoprecipitation followed by next generation sequencing we identified binding to promoter regions of 1540 and 823 genes, respectively, and showed correlation betweenBRD1-沙BRD1-l基因表达的结合和调节。确定的BRD1发现交互网络主要与BRD1mRNA in the human brain and enriched for pathways involved in gene expression and brain function. By interrogation of large datasets from genome-wide association studies, we further demonstrate that theBRD1interaction network is enriched forschizophrenia风险。 我们的结果表明BRD1interacts with chromatin remodeling proteins, e.g. PBRM1, as well as histone modifiers, e.g. MYST2 and SUV420H1. We find thatBRD1primarily binds in close proximity to transcription start sites and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate thatBRD1acts as a regulatory hub in a comprehensiveschizophreniarisk network which plays a role in many brain regions throughout life, implicating e.g. striatum, hippocampus, and amygdala at mid-fetal stages. |
| SCZ Keywords | schizophrenia |