Epigenetic mechanism in autism disorder

自闭症的表观遗传机制

• 批准号: 23791156
• 负责人: MIYAKE Kunio
• 金额: $ 2.66万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791156/
• 关键词: エピジェネティクス; 遺伝子発現; レット症候群; 自閉症; MeCP2; DNAメチル化; 発達障害; シナプス; ヒストン修飾

Rett syndrome is a neurodevelopmental and autistic disease caused by mutations of Methyl-CpG-binding protein 2 (MECP2) gene. MeCP2 protein binds to methylated gene promoters to suppress their expression, indicating that Rett syndrome is caused by the deregulation of target genes. However, it is likely that there are more unidentified neuronal MeCP2-targets associated with the neurological features of RTT. Using a genome-microarray approach, we found 22 genomic regionsthat contain sites potentially regulated by MeCP2. Within these regions, Chromatinimmunoprecipitation (ChIP) analysis revealed that MeCP2 binds to the upstream regions of the LIN7A, PCDHB1 and PCDH7. Since these genes are generally essential for brain development, aberrant regulation of these molecules may contribute to the pathogenesis of the neurological features observed in Rett syndrome.

Rett综合征是一种由甲基cpg结合蛋白2 （MECP2）基因突变引起的神经发育和自闭症疾病。MeCP2蛋白结合甲基化基因启动子抑制其表达，提示Rett综合征是由靶基因失调控引起的。然而，与RTT的神经学特征相关的未知的神经元mecp2靶点可能更多。使用基因组微阵列方法，我们发现22个基因组区域包含可能受MeCP2调控的位点。在这些区域内，染色质免疫沉淀（ChIP）分析显示MeCP2结合到LIN7A、PCDHB1和PCDH7的上游区域。由于这些基因通常是大脑发育所必需的，这些分子的异常调节可能有助于Rett综合征中观察到的神经学特征的发病机制。

项目成果

The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome.

• DOI: 10.1186/1471-2202-12-81
• 发表时间: 2011-08-08
• 期刊: BMC neuroscience
• 影响因子: 2.4
• 作者: Miyake K;Hirasawa T;Soutome M;Itoh M;Goto Y;Endoh K;Takahashi K;Kudo S;Nakagawa T;Yokoi S;Taira T;Inazawa J;Kubota T
• 通讯作者: Kubota T

Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders.

神经发育障碍的表观遗传机制和治疗前景。

• 发表时间: 2012
• 期刊: Pharmaceuticals
• 影响因子: 4.6
• 作者: Kubota T;Hirasawa T;Miyake K.
• 通讯作者: Miyake K.

Corticosterone facilitates the synchronized calcium oscillation in hippocampal neurons

皮质酮促进海马神经元的同步钙振荡

• 发表时间: 2011
• 作者: T. Hirasawa;A Endo;K. Miyake;S. Koizumi;T. Kubota
• 通讯作者: T. Kubota

Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics.

• DOI: 10.1186/1868-7083-4-1
• 发表时间: 2012-01-20
• 期刊: Clinical epigenetics
• 影响因子: 5.7
• 作者: Kubota T;Miyake K;Hirasawa T
• 通讯作者: Hirasawa T

精神疾患のエピジェネティクス:メチル化 CpG 結合蛋白(MeCP2)研究の最近の動向

精神疾病的表观遗传学：甲基化 CpG 结合蛋白 (MeCP2) 研究的最新趋势

• 发表时间: 2011
• 作者: 三宅邦夫;久保田健夫
• 通讯作者: 久保田健夫