Epigenetic mechanism in autism disorder

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791156
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: University of Yamanashi
• Principal Investigator: MIYAKE Kunio 山梨大学, 医学工学総合研究部, 助教 (60550712)
• Project Period (FY): 2011 – 2012
• Keywords: エピジェネティクス / 遺伝子発現 / レット症候群 / 自閉症

Research Abstract

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.

Research Products

• [Journal Article] Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics. Clin (2012)
  • Author(s): Kubota,T., Miyake,K. and Hirasawa, T
  • Journal Title: Epigenetics Volume: 4
  • Peer Reviewed
• [Journal Article] Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders (2012)
  • Author(s): Kubota,T, Hirasawa,T. and Miyake,K
  • Journal Title: Pharmaceuticals Volume: 5 Pages: 369-383
  • Peer Reviewed
• [Journal Article] The protocadherins, PCDHB1and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome (2011)
  • Author(s): Miyake, K., Hirasawa, T., Soutome, M., Itoh, M., Goto, Y., et al
  • Journal Title: BMC Neurosci Volume: 12 Pages: e81
  • Peer Reviewed
• [Presentation] Identification of MeCP2-target synaptic molecules associated with pathogenesis of Rett syndrome (2011)
  • Author(s): Miyake K, Hirasawa T, Taira T, Kubota T
  • Organizer: 23th Biennial Meeting,International Society for Neurochemistry jointly with the European Society for Neuroscience
  • Place of Presentation: Athens, Greece
  • Year and Date: 20110800
• [Presentation] Corticosterone facilitates the synchronized calcium oscillation in hippocampal neurons (2011)
  • Author(s): Hirasawa T, Endo A, Miyake K, Koizumi S, Kubota T
  • Organizer: 23th Biennial Meeting,International Society for Neurochemistry jointly with the European Society for Neuroscience
  • Place of Presentation: Athens, Greece
  • Year and Date: 20110800
• [Book] 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 (2011)
  • Author(s): 三宅邦夫、久保田健夫
  • Total Pages: 6-11
  • Publisher: 先端医学社
• [Book] 精神発達遅滞・自閉症の分子医学 既知の遺伝子異常による発達障害・精神遅滞の分子医学 6. レット症候群の分子医学) (2011)
  • Author(s): 三宅邦夫, 久保田健夫
  • Total Pages: 639-644
  • Publisher: 医学のあゆみ
• [Book] Chapter7: Epigenetics in autism and other neurodevelopmental diseases. In "Neurodegenerative Diseases"(Madae Curie Bioscience Databases)、ISBN 978-953-307-259-3 (2011)
  • Author(s): Miyake K, HirasawaT, Koide T, KubotaT
  • Publisher: Landes Bioscience