Roles of Chromatin Protein HIM-17 in Chromosome Structure and Function

染色质蛋白 HIM-17 在染色体结构和功能中的作用

• 批准号: 7513022
• 负责人: JESSICA B Bessler
• 金额: $ 13.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-10 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7513022
• 关键词: Affect; Alleles; Aneuploidy; Antibodies; Binding Proteins; Biochemistry; Biological; Biological Assay; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Candidate Disease Gene; Cell Proliferation; Cell physiology; Cells; Cellular biology; Chromatin; Chromatin Structure; Chromosome Structures; Chromosomes; Complement; Congenital Abnormality; DNA; Data; Depth; Equilibrium; Failure; Gene Chips; Genes; Genetic; Genetic Transcription; Genome Stability; Germ Cells; Germ Lines; Goals; Growth; High temperature of physical object; Histone H3; Human; Immunoprecipitation; Laboratories; Lysine; Mass Spectrum Analysis; Meiosis; Methylation; Modification; Mutation; Notch Signaling Pathway; Pathway interactions; Phenotype; Process; Property; Proteins; Regulation; Research; Research Personnel; Role; Signal Transduction; Site; Spontaneous abortion; Sterility; Structure; Testing; Tumor Suppressor Proteins; Universities; Work; X Chromosome; base; chromatin protein; histone methyltransferase; insight; mutant; notch protein; novel; professor; programs; protein function; research study; segregation; tumor; tumor growth

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is to understand how chromosome and chromatin structures control essential cellular processes. Changes in chromosome and chromatin structures can affect the ability of DNA and chromatin binding proteins to associate with their sites of action, thereby providing a mechanism by which to regulate transcription, signaling, and genome-stability pathways. To further our understanding of these chromosome-based control mechanisms, the current application will focus on the C. elegans protein HIM-17, a chromatin-associated protein that is proposed to function as a global chromatin organizer. HIM-17 is required for proper segregation of meiotic chromosomes, a process whose failure leads to aneuploid offspring, one of the leading causes of miscarriages and birth defects in humans. HIM-17 also functions in maintaining the correct balance between proliferation and differentiation of germ cells. Failure to maintain this balance can result in the formation and growth of tumors. Finally, HIM-17 is required for normal acquisition of covalent modifications of germline chromatin. The experiments proposed will investigate the mechanisms by which HIM-17 interacts with chromatin to control these essential cellular processes. The specific aims are: 1) To assess candidate HIM-17-associated proteins for roles in genome stability, chromatin methylation, and regulating the balance between germ cell proliferation and differentiation, 2) To investigate relationships between HIM-17, histone methyltransferase MET-2, and chromatin methylation in germ cells, 3) To investigate the role of HIM-17 as a tumor suppressor protein, and 4) To conduct screens to identify gene products that collaborate with or antagonize HIM-17.

描述（由申请人提供）：拟议研究的长期目标是了解染色体和染色质结构如何控制基本的细胞过程。 染色体和染色质结构的变化可以影响DNA和染色质结合蛋白与其作用位点结合的能力，从而提供调节转录、信号传导和基因组稳定性途径的机制。 为了进一步了解这些基于染色体的控制机制，目前的应用将集中在C。elegans蛋白HIM-17，一种染色质相关蛋白，被认为是一种全局染色质组织者。 HIM-17是正确分离减数分裂染色体所必需的，减数分裂染色体的过程失败会导致非整倍体后代，这是人类流产和出生缺陷的主要原因之一。 HIM-17还在维持生殖细胞的增殖和分化之间的正确平衡中起作用。 如果不能维持这种平衡，就会导致肿瘤的形成和生长。 最后，HIM-17是正常获得生殖系染色质的共价修饰所必需的。 提出的实验将研究HIM-17与染色质相互作用以控制这些基本细胞过程的机制。 具体目标是：1）评估候选HIM-17相关蛋白在基因组稳定性、染色质甲基化和调节生殖细胞增殖与分化之间的平衡中的作用，2）研究HIM-17、组蛋白甲基转移酶MET-2和生殖细胞中染色质甲基化之间的关系，3）研究HIM-17作为肿瘤抑制蛋白的作用，和4）进行筛选以鉴定与HIM-17协同或拮抗的基因产物。