MARC Predoctoral Fellowship Program

MARC 博士前奖学金计划

• 批准号: 7354064
• 负责人: Jenel Nixon
• 金额: $ 3.07万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7354064
• 关键词: Address; Binding; Binding Proteins; Biological Assay; Biological Models; CCL7 gene; Cell Nucleus; Chimera organism; Chromatin; Chromosome Mapping; DNA; DNA Packaging; Defect; Eukaryota; Eukaryotic Cell; Fellowship Program; Fluorescence Microscopy; Gene Deletion; Gene Expression; Gene Expression Regulation; Genes; Genome; Goals; Grant; Heterochromatin; Human; Lamins; Lead; Learning; Libraries; Localized; Mediating; Membrane Proteins; Monitor; Muscular Dystrophies; Mutation; Nuclear; Nuclear Envelope; Nuclear Lamin; Nuclear Pore; Pathway interactions; Plasmids; Positioning Attribute; Progeria; Proteins; Purpose; Role; Saccharomyces; Screening procedure; Structure; Syndrome; Transcriptional Regulation; Ubiquitin; Yeasts; base; deletion library; gene function; human disease; mutant; pre-doctoral; research study; transcription factor; yeast two hybrid system

DESCRIPTION (provided by applicant): The packaging of DNA in chromatin greatly influences gene expression. Recent findings indicate that chromatin positioning within the nucleus influences gene activity. In particular, the nuclear periphery appears to comprise a domain critical for transcriptional control. Many highly expressed genes localize to nuclear pores. Silenced chromatin also occupies a specific nuclear address. In yeast and in higher eukaryotes, silenced chromatin resides in sub-compartments at the nuclear periphery. In humans, some mutation of lamins, genes that contribute to the nuclear compartmentalization of chromatin, lead to laminopathies, including muscular dystrophy and Hutchinson-Gilford Progeria Syndrome. The goal of this proposal is to understand how chromatin organization is determined using yeast Saccharomyces as a model system. The Gartenberg lab recently showed that yeast heterochromatin is bound to the nuclear periphery by a nuclear membrane-associated protein Esc1.I aim to identify Esc1 interacting partners by adapting the split ubiquitin yeast two hybrid screen and by using and a whole genome cytological screen. I will then use silencing and DNA localization assays to learn how Esc1 contributes to the nuclear position and regulation of genes.

描述（申请人提供）：染色质中 DNA 的包装极大地影响基因表达。最近的研究结果表明，染色质在细胞核内的定位会影响基因活性。 特别是，核外围似乎包含对转录控制至关重要的结构域。 许多高表达的基因定位于核孔。 沉默的染色质也占据特定的核地址。 在酵母和高等真核生物中，沉默的染色质驻留在核外围的子区室中。 在人类中，核纤层蛋白（有助于染色质核区室化的基因）的一些突变会导致核纤层蛋白病，包括肌营养不良症和哈钦森-吉尔福德早衰综合症。 该提案的目标是了解如何使用酵母菌作为模型系统来确定染色质组织。 Gartenberg 实验室最近表明，酵母异染色质通过核膜相关蛋白 Esc1 与核外围结合。我的目标是通过采用分裂泛素酵母二杂交筛选和使用全基因组细胞学筛选来识别 Esc1 相互作用伙伴。 然后，我将使用沉默和 DNA 定位测定来了解 Esc1 如何影响基因的核位置和调节。