Transcriptional Regulation of Oocyte-Specific Genes

卵母细胞特异性基因的转录调控

• 批准号: 6994147
• 负责人: Jia L Song
• 金额: $ 5.36万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6994147
• 关键词: computational biology; developmental genetics; gel mobility shift assay; gene expression; genetic regulation; genetic regulatory element; genetic transcription; mathematical model; oogenesis; polymerase chain reaction; postdoctoral investigator; sea urchins

DESCRIPTION (provided by applicant): An oocyte undergoes a prolonged developmental process. From a primordial germ cell, oocytes develop into fertilizable eggs with specialized organelles and structures that function uniquely at fertilization. The objective of this research is to elucidate the molecular mechanism of the oocyte developmental program by examining transcriptional controls of oocyte-specific genes. I hypothesize that oocytes utilize a transcriptional network that controls the coordinated expression of oocyte-specific genes and that some of these regulatory factors will be selective for oocytes. To test this hypothesis, I will examine c/s-regulatory sequences within promoters of several oocyte-specific genes, such as those encoding unique oocyte structural proteins, enzymes, and transcription factors that are selectively enriched in the oocyte. Computational algorithms will be used to identify conserved cis-elements within oocyte gene promoters, followed by in vivo testing of transcriptional activity using reporter gene constructs. Trans-acting factors with putative binding sites within cis-elements will be identified by computational, mutational analysis, biochemical, and molecular genetic approaches. Defining transcription complexes that regulate several oocyte gene promoters will create a paradigm in gene regulatory networks that orchestrates the development of oocytes and further our knowledge in reproductive biology.

描述（由申请人提供）：卵母细胞经历一个延长的发育过程。从原始生殖细胞，卵母细胞发育成具有在受精时独特功能的专门细胞器和结构的可受精卵。本研究的目的是通过检测卵母细胞特异性基因的转录调控来阐明卵母细胞发育程序的分子机制。我假设卵母细胞利用一个转录网络，控制卵母细胞特异性基因的协调表达，这些调控因子中的一些将是卵母细胞的选择性。为了验证这一假设，我将检查几个卵母细胞特异性基因的启动子内的顺式调控序列，如那些编码独特的卵母细胞结构蛋白，酶和转录因子，选择性地富集在卵母细胞。计算算法将用于确定卵母细胞基因启动子内的保守顺式元件，然后使用报告基因构建体进行体内转录活性测试。将通过计算、突变分析、生物化学和分子遗传学方法鉴定顺式元件内具有推定结合位点的反式作用因子。定义调控几个卵母细胞基因启动子的转录复合物将在基因调控网络中创建一个范例，该网络协调卵母细胞的发育，并促进我们在生殖生物学方面的知识。