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.

我们已经讨论了DNA：RNA三螺旋形成在基因表达调控中的可能作用，特别是在人类β珠蛋白基因位点。 对于可以形成这种结构的碱基组合有严格的规则。 我们寻找符合这些规则的地点。 最重要的是，我们发现成人β珠蛋白初级转录物内的内含子序列可以与β珠蛋白基因座控制区（LCR）（β珠蛋白基因的主要正化合物调节元件）中的靶位点形成三螺旋。 我们表明，当一个完整的长度转录包含野生型第二β珠蛋白内含子过表达，它下调珠蛋白基因的表达，通过结合到一个网站的LCR和置换转录因子。相同但内含子三链体形成序列突变的转录物没有影响。这似乎是一个反馈系统，以防止β珠蛋白基因的过度表达。 我们在基因组的其他地方发现了这种调节的另一个例子，表明这可能是一种普遍的调节机制。 已经开始寻找在体内特异性识别三螺旋结构的蛋白质。