THE ROLES OF CP190 IN THE FAB-8 AND GYPSY CHROMATIN INSULATORS

CP190 在 FAB-8 和吉普赛染色质绝缘体中的作用

• 批准号: 7959718
• 负责人: Chi-Yun Pai
• 金额: $ 12.88万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959718
• 关键词: Binding Sites; Biomedical Research; CCCTC-binding factor; Cell Nucleus; Chromatin; Chromatin Structure; Cloning; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA Sequence; DNA-Binding Proteins; Drosophila melanogaster; Drug Delivery Systems; Epigenetic Process; Funding; Gene Expression; Gene Expression Regulation; Genomic Imprinting; Goals; Grant; Gypsies; Human; Huntington Disease; Institution; Knowledge; Lead; Malignant Neoplasms; Molecular; Mutation; Neurologic; Pharmaceutical Preparations; Proteins; Recruitment Activity; Reporting; Research; Research Personnel; Resources; Role; Source; Testing; Therapeutic; Tumor Suppression; Tumor Suppressor Proteins; United States National Institutes of Health; Wing; Zinc Fingers; design; insight; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The gypsy chromatin insulator of Drosophila melanogaster is the best understood insulator to date. It is a DNA sequence containing 12 copies of a binding site for the DNA-binding protein Suppressor of Hairy-wing [Su(Hw)] which recruits other insulator proteins to organize the insulator complex. We reported that the centrosomal protein CP190 is an essential component of the gypsy insulator. It was recently discovered that CP190 is also present in the Fab-8 insulator complex which depends on the DNA-binding protein CTCF instead of Su(Hw). CTCF has important roles on epigenetic control of gene expression and is a human tumor suppressor. Current evidence indicates that CP190 has essential functions in multiple types of insulators and may be involved in genetic imprinting and tumor suppression. The main goals of this proposal are to: 1) Determine the function of CP190's protein sub-domains in gypsy and Fab-8 insulator complexes; 2) Identify the target DNA sequences of CP190's zinc fingers; 3) Identify additional chromatin insulator components by cloning two novel insulator mutations. The proposed studies will investigate a fundamental question concerning chromatin organization and the regulation of gene expression in the cell nucleus. We will gain insights into the molecular mechanisms through which chromatin insulators regulate gene expression, and more generally, chromatin structure and organization of the cell nucleus. Currently drugs are being tested that target chromatin regulators as a therapeutic approach to cancers and to untreatable neurological conditions like Huntington disease. More detailed knowledge of the basic mechanisms of chromatin insulators could lead to better design of new treatments and may lead to discovery of new drug targets.

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