Toxoplasma Epigenomics and Gene Expression

弓形虫表观基因组学和基因表达

基本信息

批准号：
8432851
负责人：
Kami Kim
金额：
$ 67.9万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
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：
2010-03-15 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8432851
关键词：
Acquired Immunodeficiency Syndrome Affect Apicomplexa Biological Assay Cell Cycle Cells ChIP-on-chip Chromatin Chromatin Remodeling Factor Chromatin Structure Clinical Complex Cryptosporidium DNA DNA Binding Development Disease Drug Targeting Encephalitis Environment Epidemic Epigenetic Process Event Family Family member Gene Activation Gene Expression Gene Expression Regulation Gene Structure General Transcription Factors Genes Genetic Genome Genomics Genotype Immune system Immunocompromised Host Individual Infection Lead Life Cycle Stages Macromolecular Complexes Mammals Maps Metabolism Modeling Molecular Mutagenesis Opportunistic Infections Organism Parasites Pathogenesis Patients Pattern Plant Genes Plants Protein Binding Proteins Proteomics Role Specificity Stress Surface Antigens Systems Biology TFAP2A gene Testing Toxoplasma Toxoplasma gondii Toxoplasmosis Transcription Factor AP-2 Alpha Virulence Work base chromatin modification combinatorial epigenome epigenomics interdisciplinary approach obligate intracellular parasite pathogen preference prevent programs promoter public health relevance response scaffold trait transcription factor

项目摘要

DESCRIPTION (provided by applicant): The obligate intracellular parasite Toxoplasma gondii is a major opportunistic pathogen of the AIDS epidemic. As it develops within host cells, the parasite implements a coordinated pattern of sequential gene expression. In response to stress and changes in its environment, the parasite completely alters its metabolism, surface antigens, and cell cycle to transition from tachyzoite to bradyzoite. Understanding how T. gondii regulates gene expression is fundamental for understanding the pathogenesis of toxoplasmosis. Epigenetic factors govern developmental transitions and expression of virulence traits, and are also implicated in T. gondii bradyzoite differentiation. How chromatin remodeling complexes interact with transcriptional machinery in T. gondii is not known. Recently, a plant-like transcription factor family, the APETELA 2 (or AP2) family, has been discovered and proposed as the primary transcription factors of T. gondii and other Apicomplexa. We hypothesize that conserved Apicomplexa AP2 family members have conserved functions in T. gondii as sequence-specific transcription factors that interact with general transcription factors and chromatin remodeling complexes to regulate gene expression. We have previously developed a epigenomic map of tachyzoites that defines functional regions of the genome. We will use this prior work to assist us in determining the genes regulated by TgAP2. The DNA binding specificity of AP2 proteins will be identified using a multidisciplinary approach. Proteins that interact with TgAP2 will be identified using proteomics. These studies will form a scaffold upon which we will build systems biology model to understand how gene networks govern biologically significant events such as bradyzoite formation.

描述（由申请人提供）：专性细胞内寄生虫弓形虫弓形虫是艾滋病流行病的主要机会病原体。随着它在宿主细胞内的发展，寄生虫实现了顺序基因表达的协调模式。为了应对压力和环境的变化，寄生虫完全改变了其新陈代谢，表面抗原和细胞周期，从tachyzoite转变为bradyzoite。了解T. gondii如何调节基因表达对于理解弓形虫病的发病机理至关重要。表观遗传因素控制毒力性状的发育过渡和表达，也与弓形虫链球菌分化有关。尚不清楚染色质重塑复合物与T. gondii中的转录机械相互作用。最近，已经发现并提出了一个类似植物的转录因子家族，即Apetela 2（或AP2）家族，并提出是T. gondii和其他Apicomplexa的主要转录因子。我们假设保守的APICOMPLEXA AP2家族成员在T. gondii中具有保守的功能，作为序列特异性转录因子，与一般转录因子相互作用和染色质重塑复合物相互作用以调节基因表达。我们以前已经开发了速氮族的表观基因组图，该图定义了基因组的功能区域。我们将使用这项先前的工作来帮助我们确定由TGAP2调节的基因。将使用多学科方法鉴定AP2蛋白的DNA结合特异性。将使用蛋白质组学鉴定与TGAP2相互作用的蛋白质。这些研究将形成一个脚手架，我们将建立系统生物学模型，以了解基因网络如何控制生物学意义的事件，例如牛曲菌形成。