Regulation Of Erythroid Gene Expression

红系基因表达的调控

• 批准号: 10248115
• 负责人: Gary Felsenfeld
• 金额: $ 14.38万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10248115
• 关键词: Address; Adult; Binding; DNA; Erythroid; Feedback; Gene Expression; Gene Expression Regulation; Genes; Genome; Globin; Human; Introns; Length; Locus Control Region; Mutate; Nucleic Acids; Proteins; RNA; Regulation; Regulatory Element; Role; Site; Structure; System; Transcript; Work; base; beta Globin; genomic locus; in vivo; overexpression; prevent; transcription factor; triple helix

We have addressed the possible role of DNA:RNA triple helix formation in regulation of gene expression, particularly in the human beta globin gene locus. There are strict rules for the combinations of bases that can form such structures. We searched for loci that obeyed those rules. Most significantly we have found that an intronic sequence within the adult human beta globin primary transcript can form a triple helix with a target site in the beta globin locus control region (LCR), the major positive compound regulatory element of the beta globin genes. We show that when a full length transcript containing the wild type second beta globin intron is overexpressed it downregulates expression of globin genes by binding to a site in the LCR and displacing transcription factors. A transcript that is identical but with the intronic triplex forming sequence mutated has no effect. This appears to be a feedback system to prevent overexpression of the beta globin genes. We have found another example of this regulation elsewhere in the genome, suggesting that this may a general regulatory mechanism. Work has begun to search for proteins that specifically recognize triple helical structures in vivo.

我们已经解决了DNA的可能作用：RNA三重螺旋形成在基因表达的调节中，特别是在人β球蛋白基因基因座中。 对于可以形成此类结构的基础组合有严格的规则。 我们搜索了遵守这些规则的基因座。 最重要的是，我们发现成年人类β球蛋白主要转录本内的内含子序列可以在β球蛋白基因座控制区域（LCR）中形成三重螺旋，这是β球蛋白基因的主要阳性复合元件。 我们表明，当包含野生型第二β球蛋白内含子的全长转录本过表达时，它通过与LCR中的位点结合并置换了转录因子来下调球蛋白基因的表达。相同但内含子三形形成序列突变的转录本没有影响。这似乎是防止β球蛋白基因过度表达的反馈系统。 我们发现了基因组其他地方的该调节的另一个例子，表明这可能是一种普遍的调节机制。 工作已经开始寻找特殊识别体内三重螺旋结构的蛋白质。