Downstream Targets of Olig 2

Olig 2 的下游靶标

基本信息

批准号：
7488486
负责人：
SHWETAL MEHTA
金额：
$ 5.01万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7488486
关键词：
Acute Adult Animals Antibodies BHLH Protein Binding Binding Sites Biochemical Biological Brain Brain Neoplasms Cell Line Cell Nucleus Cells Chimeric Proteins Chromosomes, Human, Pair 21 Complement Coupling Cytosol DNA Dana-Farber Cancer Institute Data Development Disease Emerging Technologies Employee Strikes Estrogen Receptors Fellowship Gene Expression Profile Gene Expression Profiling Gene Targeting Genes Genetic Genetic Screening Genetic Transcription Genome Glioma Goals Human Human Chromosomes Individual Intercistronic Region Malignant Glioma Methods Molecular Molecular Profiling Multiple Sclerosis Mus Mutant Strains Mice Names Neuroepithelial Cells Neurons Nuclear Olig2 protein Oligodendroglia Personal Satisfaction Phenotype Promoter Regions Proteins Publishing Repetitive Sequence Reporting Research Risk Role Running Site Source Steroids Tamoxifen Technology Time Transcription Coactivator Transcriptional Regulation Transgenic Mice Tumor Cell Line Work chromatin immunoprecipitation expression vector in vivo loss of function neoplastic cell nerve stem cell post-doctoral training postnatal pre-doctoral programs protein function response transcription factor

项目摘要

DESCRIPTION (provided by applicant): During development, a pair of basic helix-loop-helix transcription factor, Olig1 and Olig2 regulates fate choice decisions of neural progenitor cells to form neurons or oligodendrocytes. In the adult brain, these same two transcription factors appear to have functional roles in glial disease states such as multiple sclerosis and malignant glioma. Despite the crucial role of Olig genes in glial fate decisions, the molecular mechanism(s) by which Olig genes exert these important functions are largely unresolved. To this point, there has been no report of any direct downstream genetic target, which is either expressed or repressed by Olig proteins. The broad goal of this project is to identify direct downstream genetic targets of Olig2 specifically by achieving the following two aims: 1) a genome-wide screen of DNA regions associated with Olig2 in tumor cell lines and 2) gene expression profiling of genes regulated by Olig2 in presence of conditionally expressed Olig2 protein. In short run the target genes will reveal the biochemical function of Olig2 in transcription regulation. Eventually, these target genes might have practical overtones for targeted therapy of glioma or multiple sclerosis.

描述（由申请人提供）：在开发过程中，Olig1和Olig2在开发过程中，OLIG1和OLIG2调节神经祖细胞的命运选择决策以形成神经元或少突胶质细胞。在成年大脑中，这两个相同的转录因子似乎在神经胶质疾病状态（例如多发性硬化症和恶性神经胶质瘤）中具有功能作用。尽管寡核基因在神经胶质命运决策中的作用至关重要，但寡核基因发挥这些重要功能的分子机制在很大程度上尚未解决。至此，还没有任何直接下游遗传靶标的报道，该遗传靶标由olig蛋白表达或抑制。该项目的广泛目标是通过实现以下两个目的来鉴定OLIG2的直接下游遗传靶标：1）在肿瘤细胞系中与Olig2相关的DNA区域的全基因组筛选和2）在有条件表达的OLIG2蛋白下，由Olig2调节的基因表达分析。简而言之，靶基因将揭示基2在转录调控中的生化功能。最终，这些靶基因可能对胶质瘤或多发性硬化症的靶向治疗有实用的色彩。