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Molecular Dissection of Drosophila Hox Gene Cis-Regulatory Modules

果蝇 Hox 基因顺式调控模块的分子解剖

基本信息

批准号：
8877979
负责人：
ROBERT A DREWELL
金额：
$ 2.89万
依托单位：
CLARK UNIVERSITY (WORCESTER, MA)
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8877979
关键词：
Molecular Dissection Drosophila Hox Gene

项目摘要

Project Summary How are key genes in our DNA regulated? How is their expression coordinated in the proper space and time during embryonic development? These questions have enormous implications in our comprehension of the developmental program in animals and humans. Despite this fact, our current understanding of regulation of gene expression at the molecular level remains somewhat superficial. It has been shown that the transcription of critical developmental genes is controlled in a variety of ways by specific regions of neighboring non‐coding genomic DNA sequences. These distinct cis‐regulatory modules (CRMs), which include transcriptional enhancers, insulators, and silencers, have been found to regulate gene expression in all the model eukaryotic systems studied so far. In some cases, specific transcription factors have been found to bind at sequences in the CRMs and to regulate their activity. However, the molecular mechanisms that determine where transcription factors bind within most CRM sequences and how this binding regulates CRM function remain unclear. The Hox genes of the Drosophila bithorax complex are critical genes that determine the animal body plan during embryonic development. The expression of Hox genes spatially and temporally in the developing embryo is controlled by CRMs. Our initial studies show that sequences at the CRMs of the Drosophila bithorax complex are rapidly evolving within the Drosophila genus. This is in sharp contrast to the Hox genes, which are conserved across all bilaterian animals. The large set of known enhancer CRMs at the Drosophila bithorax complex, and the rapid evolution of the sequences at these CRMs across different Drosophila species, provide an exciting opportunity to study the relationship between sequences at the CRMs, transcription factor binding and cis‐regulatory function. The ultimate goal of this proposal is to elucidate the molecular mechanisms which control functional activity of the enhancer CRMs at the sequence level. Our proposed studies will also provide insight into the evolution of cis‐regulatory function across different species. The long term scientific goal of the PI is to fully investigate the molecular mechanisms by which the regulatory regions achieve coordinated control of gene expression across the entire bithorax complex. The major focus of this proposal will be on the bioinformatic identification and functional characterization of specific transcription factor binding sites within known CRMs of the Drosophila bithorax complex. Further experiments to test conserved sub‐regions of known CRMs for functional activity and to investigate the functional compatibility of CRM sub‐regions from distantly related Drosophila species will shed light on the evolution of CRM architecture and functional activity.

项目概要 DNA 中的关键基因是如何受到调控的？他们的表达如何在适当的空间内协调以及胚胎发育的时间？这些问题对于我们来说有着巨大的影响理解动物和人类的发育程序。尽管如此，我们目前的对分子水平上基因表达调控的理解仍有些许不足浅。研究表明，关键发育基因的转录受控于通过邻近非编码基因组 DNA 序列的特定区域以多种方式进行检测。这些不同的顺式调控模块（CRM），包括转录增强子、绝缘子和已发现沉默子可以调节所有模型真核系统中的基因表达研究到目前为止。在某些情况下，已发现特定的转录因子与以下序列结合： CRM 并规范其活动。然而，决定位置的分子机制转录因子在大多数 CRM 序列中结合，以及这种结合如何调节 CRM 功能仍不清楚。果蝇双胸复合体的Hox基因是决定动物体的关键基因胚胎发育期间的计划。 Hox基因在空间和时间上的表达发育中的胚胎由 CRM 控制。我们的初步研究表明 CRM 上的序列果蝇双胸复合体在果蝇属内迅速进化。这是锐利的与 Hox 基因相反，Hox 基因在所有两侧对称动物中都是保守的。大集合果蝇 bithorax 复合体中已知的增强子 CRM，以及序列的快速进化在不同果蝇物种的这些 CRM 中，提供了一个令人兴奋的机会来研究 CRM 序列、转录因子结合和顺式调控之间的关系功能。该提案的最终目标是阐明控制的分子机制增强子 CRM 在序列水平上的功能活性。我们提出的研究还将提供对不同物种顺式调节功能进化的深入了解。长期来看 PI 的科学目标是充分研究调控的分子机制区域实现整个胸腔复合体基因表达的协调控制。这该提案的主要重点将是生物信息识别和功能果蝇已知 CRM 中特定转录因子结合位点的表征双胸复合体。进一步的实验来测试已知 CRM 的保守子区域的功能活动并研究远亲关系的 CRM 子区域的功能兼容性果蝇物种将揭示 CRM 架构和功能活动的演变。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Global sensitivity analysis of a dynamic model for gene expression in Drosophila embryos.

果蝇胚胎基因表达动态模型的全局敏感性分析。

DOI：
10.7717/peerj.1022
发表时间：
2015
期刊：
PeerJ
影响因子：
2.7
作者：
McCarthy,GregoryD;Drewell,RobertA;Dresch,JacquelineM
通讯作者：
Dresch,JacquelineM

Parent-of-origin effects on genome-wide DNA methylation in the Cape honey bee (Apis mellifera capensis) may be confounded by allele-specific methylation.

DOI：
10.1186/s12864-016-2506-8
发表时间：
2016-03-12
期刊：
BMC genomics
影响因子：
4.4
作者：
Remnant EJ;Ashe A;Young PE;Buchmann G;Beekman M;Allsopp MH;Suter CM;Drewell RA;Oldroyd BP
通讯作者：
Oldroyd BP

Whole-genome DNA methylation profile of the jewel wasp (Nasonia vitripennis).