GENOMIC PLASTICITY IN THE HUMAN U2 SNRNA GENE CLUSTER

人类 U2 SNRNA 基因簇的基因组可塑性

• 批准号: 2180957
• 负责人: ALAN M WEINER
• 金额: $ 24.77万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2180957
• 关键词: GENOMIC; PLASTICITY; HUMAN; U2; SNRNA

DESCRIPTION: (Adapted from the application.) The genes encoding U2 small nuclear RNA (snRNA) exist as a perfect tandem array of 5 to >22 copies of a 5.8 KB repeat unit on human chromosome 17q21. This locus is a fragile site which may be induced by adenovirus 12 infection. Further, the locus has been maintained at its present site for >35 Myr through multiple speciation events in the primate lineage. The Principal Investigator proposes a multi-faceted approach to understanding adenovirus-induced chromosome fragility. Six specific aims include: (1) U2 chromosomal sequences required for fragile site induction will be identified and analyzed; (2) The chromosomal functions required for adeno 12 virus fragility will be identified, including requirements for snRNA transcription, chromatin structure, methylation, topoisomerase binding, and the origin and scheduling of replication; (3) The requirement for a high concentration of transcription units for the existence of a fragile site will be determined; (4) The evolutionary history of this primate locus will be traced. DNA sequencing from a variety of primates, as well as human groups, will be performed to compare and investigate mechanisms of inheritance and linkage; (5) The influence of U2 repeat sequences on the rate, boundaries, and stability of gene amplification will be investigated; and (6) The domains and functions of the adenovirus 12 E1B 55 kDa protein which are required for inducing chromosome fragility will be characterized.

描述：（从应用程序改编。）编码U2的基因 小核RNA（snRNA）以5至> 22的完美串联阵列存在 人类17q21上的5.8 kb重复单元的副本。这个基因座 是一个脆弱的部位，可能由腺病毒12感染诱导。 此外，该基因座在目前的现场维持> 35 MYR 通过灵长类动物血统中的多个物种事件。这 首席研究者提出了一种多方面的理解方法 腺病毒引起的染色体脆弱性。六个具体目标包括： （1）脆弱部位诱导所需的U2染色体序列将 可以识别和分析； （2）所需的染色体功能 将确定Adeno 12病毒脆弱性，包括 SnRNA转录，染色质结构，甲基化，拓扑异构酶 绑定，以及复制的起源和计划； （3） 要求高浓度的转录单元 将确定脆弱的位点的存在； （4）进化 这个灵长类动物基因座的历史将被追溯到。 DNA测序来自 各种灵长类动物以及人类群体将进行 比较和研究继承和联系的机制； （5） U2重复序列对速率，边界和稳定性的影响 将研究基因扩增； （6）域和 腺病毒12 E1B 55 kDa蛋白的功能是必需的 诱导染色体脆性将被表征。