A core transcription factor complex of the aryl hydrocarbon receptor

芳烃受体的核心转录因子复合物

• 批准号: 10393640
• 负责人: THOMAS R SUTTER
• 金额: $ 21.53万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-16 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393640
• 关键词: ARID4B gene; ARNT gene; Aging; Architecture; Aromatic Polycyclic Hydrocarbons; Aryl Hydrocarbon Receptor; Binding; Binding Proteins; Binding Sites; Biological Process; CYP1A1 gene; Cell Line; Cell physiology; Cells; Chemical Exposure; Chromatin; Complex; Congenital Abnormality; Cytochrome P450; DNA Sequence; Data; Dioxins; Disease; Elements; Encyclopedia of DNA Elements; Environmental Pollutants; Enzymes; Family; Gene Expression; Genetic Transcription; Genome; Goals; Health; HepG2; Homeostasis; Human Cell Line; Human Genome; Immunosuppression; Knowledge; Ligands; Malignant Neoplasms; Nucleotides; Pathologic; Physiological; Proteins; Regulation; Research Project Grants; Resolution; Role; Signal Pathway; Site; Testing; Toxic effect; Transcriptional Regulation; Xenobiotics; chromatin immunoprecipitation; design; epigenomics; genome-wide; improved; inducible gene expression; member; receptor; response; transcription factor

The objective of this project is to investigate a core transcription factor (TF) complex of the AHR (aryl hydrocarbon receptor) that we discovered by analysis of high-content Chromatin Immunoprecipitation-DNA Sequence (ChIP-Seq) data of the Encyclopedia of DNA Elements (ENCODE) project, a public research project to identify all functional elements in the human genome. In this project we will validate this complex, determine its physical organization and function, and evaluate whether this complex is conserved across cells and species. The AHR is best known as a ligand-activated transcription factor (TF) with important roles in the toxicity of dioxin-like compounds (DLCs) including cancer, birth defects and immunosuppression, and the regulation of enzymes such as the cytochrome P450 family 1 members that can activate procarcinogens. Moreover, recent studies demonstrate key roles of the AHR in the regulation of cell homeostasis, differentiation, aging and cancer. In this exploratory project we propose two specific aims: Aim 1. Validate the core TF complex of the AHR and determine its function and conservation across cells and species. Aim 2. Elucidate the regulatory mechanisms and biological functions of the core TF complex of the AHR. Together, these proposed studies should markedly improve the fundamental knowledge of the mechanisms impacting AHR-regulated transcription towards the long-term goal of understanding how this receptor contributes to important cellular processes in health and disease.

本课题的目的是研究AHR（aryl）的核心转录因子（TF）复合物， 碳氢化合物受体），我们通过分析高含量的染色质免疫沉淀-DNA DNA元件百科全书（ENCODE）项目的序列（ChIP-Seq）数据，一个公共研究项目 来识别人类基因组中所有的功能元件。在这个项目中，我们将验证这个复杂的，确定 它的物理组织和功能，并评估这种复合物是否在细胞间保守， 物种AHR最为人所知的是作为配体激活的转录因子（TF），其在以下过程中具有重要作用： 二恶英类化合物的毒性，包括癌症、出生缺陷和免疫抑制，以及 调节酶，如细胞色素P450家族1成员，可激活原致癌物。 此外，最近的研究表明AHR在调节细胞稳态中的关键作用， 分化、衰老和癌症。在这个探索性项目中，我们提出了两个具体目标：目标1。验证 AHR的核心TF复合物，并决定其功能和跨细胞和物种的保护。目标2. 阐明AHR核心TF复合物的调节机制和生物学功能。在一起， 这些拟议中的研究应能显著地提高对影响大气环境的机制的基本认识， AHR调节的转录朝着了解这种受体如何有助于 健康和疾病中重要的细胞过程。