Topology of the Hosthogen Genome

Hosthogen 基因组的拓扑结构

• 批准号: 8659940
• 负责人: JJ Miranda
• 金额: $ 28.65万
• 依托单位: J. DAVID GLADSTONE INSTITUTES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8659940
• 关键词: Acquired Immunodeficiency Syndrome; Address; B-Lymphocytes; Biological Assay; CCCTC-binding factor; Cell Culture Techniques; Cell Nucleus; Cells; Chromatin; Chromosomes; Cytolysis; DNA; Data; Development; Drug Targeting; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genome; HIV; Herpesviridae; Human; Human Chromosomes; Human Genome; Human Herpesvirus 4; Immune system; Infection; Life; Lymphoma; Lytic Phase; Malignant Neoplasms; Maps; Measures; Mediating; Methods; Modeling; Phase; Proteins; Protocols documentation; Published Comment; RNA; Regulatory Element; Repression; Structure; Survivors; Techniques; Time; Transcriptional Regulation; Viral; Viral Genes; Viral Genome; Virus; Virus Diseases; Work; deep sequencing; genome-wide; innovation; pathogen; promoter; public health relevance; research study; transcriptome sequencing

DESCRIPTION: The human genome is not a linear sequence, but rather a contorted knot of chromosomes in the three- dimensional space of the nucleus. Chromosomes do not work in isolation. Long-range interactions regulate gene expression. This innovation, however, has not been applied to viral infections. We still talk of host and pathogen genomes as if they are independent. I contend that these genomes are not separate, but rather an intertwined entity best referred to as a "hosthogen" genome. I propose to study long-range interactions between the human genome and latent Epstein-Barr virus (EBV). We will focus on connections mediated by the CCCTC-binding factor, a protein known to assemble interchromosomal loops. We have developed a method, the associated chromatin trap assay followed by deep sequencing (ACT-seq), to detect intergenome loops in a cell culture model of lymphoma. Persistent infection with EBV drives the development of cancer in AIDS survivors. This work may thus identify new drug targets that control viral genes responsible for HIV-associated malignancies.

描述：人类基因组不是线性序列，而是细胞核三维空间中染色体的扭曲结。染色体不能孤立地工作。长程相互作用调节基因表达。然而，这项创新尚未应用于病毒感染。我们仍然谈论宿主和病原体基因组，好像它们是独立的。我认为这些基因组不是独立的，而是一个交织在一起的实体，最好被称为“宿主”基因组。 我建议研究人类基因组和潜伏性EB病毒（EBV）之间的远程相互作用。我们将重点关注由CCCTC结合因子介导的连接，CCCTC结合因子是一种已知的组装染色体间环的蛋白质。我们已经开发了一种方法，相关的染色质陷阱测定，然后进行深度测序（ACT-seq），以检测淋巴瘤细胞培养模型中的基因组间环。EB病毒的持续感染驱动艾滋病幸存者癌症的发展。因此，这项工作可能会确定新的药物靶点，控制病毒基因负责艾滋病毒相关的恶性肿瘤。