Nuclear, Genomic and Molecular Regulation of Type I Interferon Transcription

I 型干扰素转录的核、基因组和分子调控

• 批准号: 8660635
• 负责人: Tae Hoon Kim
• 金额: $ 1.55万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8660635
• 关键词: Affect; Animal Model; Antiviral Agents; Antiviral Response; Autoimmunity; Cells; Chromatin; Chromosomes; Dendritic Cells; Developmental Gene; Diploidy; Disease; Distal; Enhancers; Epigenetic Process; Fiber; Fibroblasts; Foundations; Gene Activation; Genes; Genetic Transcription; Genome; Genomics; Goals; Human; Human Genome; Image; Immune response; Immune system; Inflammatory; Interferon Activation; Interferon Type I; Interferon-beta; Interferons; Kinetics; Link; Location; Mediating; Methods; Microscopy; Molecular; Molecular Conformation; Mus; Nuclear; Positioning Attribute; Process; Production; Property; Regulation; Regulatory Element; Research Proposals; Resolution; Role; Running; Solid; System; Techniques; Time; Transcriptional Activation; Transcriptional Regulation; Viral; Virus; Virus Diseases; cell type; cohesin; in vivo; lymphoblast; microbial; molecular imaging; novel; pathogen; promoter; public health relevance; therapeutic development; therapeutic target

DESCRIPTION (provided by applicant): Our long-term goal of this exploratory research proposal is to determine how chromosome conformation and subnuclear position affect the host response to viruses. Significance and role of large-scale nuclear processes of folding and juxtaposition of chromosomal fibers during innate immune response to viruses remain relatively unknown. However, these processes represent unexplored epigenetic targets for modulating the innate immune system for potential therapies. To understand these nuclear processes involved in anti-viral response in human cells, we will characterize the molecular mechanisms that modulate chromosomal conformation and subnuclear location of the type I interferon locus in the genome of diploid fibroblasts and lymphoblasts during viral infection. A better understanding of the regulatory mechanisms involved in the production of type I interferons is fundamental to the development of therapeutic strategies for treating viral infections and inflammatory diseases such as autoimmunity.

描述（由申请人提供）：我们这项探索性研究提案的长期目标是确定染色体构象和亚核位置如何影响宿主对病毒的反应。在对病毒的先天免疫应答期间，染色体纤维的折叠和并列的大规模核过程的意义和作用仍然相对未知。然而，这些过程代表了用于调节先天免疫系统的潜在疗法的未探索的表观遗传靶点。为了了解这些核过程中参与抗病毒反应在人类细胞中，我们将表征的分子机制，调节染色体构象和亚核位置的I型干扰素基因座的二倍体成纤维细胞和成淋巴细胞的基因组中的病毒感染。更好地理解参与I型干扰素产生的调节机制对于治疗病毒感染和炎性疾病如自身免疫的治疗策略的发展是至关重要的。