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Molecular basis of transvection

横传的分子基础

基本信息

批准号：
7268152
负责人：
Mariano Labrador-San Jose
金额：
$ 17.45万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
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：
2006-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7268152
关键词：
Address Alleles Asses Binding Proteins Biological Assay Biology Bypass Cell Nucleus Cells Chromatin Chromatin Fiber Chromatin Structure Chromosomes Computer Analysis Development Distal Drosophila genus Electrophoretic Mobility Shift Assay Enhancers Eukaryota Eukaryotic Cell Event Exhibits Female sterility Fluorescence Microscopy Gene Expression Gene Expression Regulation Genes Genetic Genetic Phenomena Genetic Transcription Genome Germ Lines Goals Gypsies Hereditary Disease Heterochromatin Homologous Gene Insulator Elements Interphase Laboratories Labrador Light Maintenance Malignant Neoplasms Mammals Maps Mediating Molecular Molecular Biology Molecular Conformation Mutation Nuclear Organism Plants Play Positioning Attribute Process Property Proteins Reporting Research Personnel Role Signal Transduction Site Structure System Testing Time Tissues Transgenic Organisms Yeasts base design genetic analysis genetic element human disease interest programs promoter research study

项目摘要

DESCRIPTION (provided by applicant): Our laboratory is interested in understanding the mechanisms presiding enhancer-promoter interactions and the role of insulators in gene expression regulation. The goal of this proposal is to explore the molecular mechanisms underlying the phenomenon of transvection. Interaction of enhancers with promoters is a critical step in the orchestrated process leading to time and tissue specific regulation of gene expression. Enhancers can specifically activate promoters even at distances longer than 100 kb. Remarkably, enhancers can also trans-activate promoters located in homologue chromosomes, a phenomenon known as transvection. Transvection depends on somatic pairing between chromosomes, wherein the expression of one gene is influenced by regulatory signals emerging from its corresponding allele on the homologue chromosome. Transvection has been very well characterized at the genetic level in Drosophila, but numerous examples reported from multiple organisms including yeasts, plants and mammals, suggest that trans-activation (i.e. transvection) is a conserved eukaryotic regulatory feature. We propose that insulators are the molecular vehicles by which enhancers can communicate with promoters located in separate chromosomes. The following two aims are designed to test this hypothesis. A: assess the ability of gypsy insulators to mediate transvection using transgenic assays. Cell and molecular biology assays as well as mutational analysis will asses the involvement of insulators in experimentally controlled transvection settings. B: assess whether there is a general role of endogenous insulators in transvection. We will map and characterize specific endogenous insulators with a predicted role in transvection using computer analysis, fluorescence microscopy, gel shift assays and transgenic assays. Genetic analysis will also assess the role that insulator proteins play in previously reported transvection phenomena. These studies might have an immediate repercussion in the general understanding of the regulatory processes involved in somatic and germ-line development. Both, transvection as well as genome insulators may be involved in the control of transcription of numerous genes and therefore have a broad impact in the biology of human diseases, including cancer. Understanding how enhancers interact with promoters and the role of insulators in this process may provide new avenues to approach the study of genetic diseases.

描述（由申请人提供）：我们的实验室对了解增强子-启动子相互作用的机制和绝缘子在基因表达调控中的作用感兴趣。本研究的目的是探讨横切现象的分子机制。增强子与启动子的相互作用是导致基因表达的时间和组织特异性调控的协调过程中的关键步骤。增强子甚至可以在超过100 kb的距离上特异性激活启动子。值得注意的是，增强子也可以反式激活位于同源染色体上的启动子，这种现象被称为transvection。横切依赖于染色体之间的体细胞配对，其中一个基因的表达受到同源染色体上相应等位基因产生的调控信号的影响。在果蝇中，转染已经在遗传水平上得到了很好的表征，但从包括酵母、植物和哺乳动物在内的多种生物中报道的大量例子表明，反式激活（即转染）是一种保守的真核生物调控特征。我们提出绝缘体是分子载体，增强子可以通过它与位于不同染色体上的启动子进行通信。以下两个目标旨在验证这一假设。答：评估吉普赛绝缘子介导转基因的能力。细胞和分子生物学分析以及突变分析将在实验控制的横切设置中评估绝缘体的参与。B：评估内源性绝缘子在横切中是否有普遍作用。我们将利用计算机分析、荧光显微镜、凝胶转移测定和转基因测定来绘制和表征特定的内源性绝缘体，并预测其在转染中的作用。遗传分析也将评估绝缘子蛋白在先前报道的横切现象中所起的作用。这些研究可能会对体细胞和种系发育中涉及的调节过程的一般理解产生直接的影响。横切和基因组绝缘子都可能参与控制许多基因的转录，因此在包括癌症在内的人类疾病的生物学中具有广泛的影响。了解增强子如何与启动子相互作用以及绝缘子在这一过程中的作用可能为遗传疾病的研究提供新的途径。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Changes in chromatin structure correlate with transcriptional activity of nucleolar rDNA in polytene chromosomes.

染色质结构的变化与多线染色体中核仁 rDNA 的转录活性相关。

DOI：
10.1007/s00412-008-0198-9
发表时间：
2009
期刊：
Chromosoma
影响因子：
1.6
作者：
Plata,MariaPiedad;Kang,HyuckJoon;Zhang,Shaofei;Kuruganti,Srilalitha;Hsu,Shih-Jui;Labrador,Mariano
通讯作者：
Labrador,Mariano

The Drosophila gypsy insulator supports transvection in the presence of the vestigial enhancer.

果蝇吉普赛绝缘体在残留增强子存在的情况下支持横传。