A core transcription factor complex of the aryl hydrocarbon receptor

芳烃受体的核心转录因子复合物

基本信息

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
项目类别：
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

项目摘要

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.

该项目的目标是研究 AHR（芳基转录因子）的核心转录因子 (TF) 复合物我们通过高含量染色质免疫沉淀-DNA 分析发现的碳氢化合物受体）公共研究项目 DNA 元素百科全书 (ENCODE) 项目的序列 (ChIP-Seq) 数据识别人类基因组中的所有功能元件。在这个项目中，我们将验证这个复合体，确定其物理组织和功能，并评估该复合物在细胞和细胞之间是否保守物种。 AHR 最为人所知的是一种配体激活转录因子 (TF)，在二恶英类化合物 (DLC) 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，可激活致癌物质。此外，最近的研究表明 AHR 在细胞稳态调节中的关键作用，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，并确定其跨细胞和物种的功能和保守性。目标2。阐明 AHR 核心 TF 复合物的调控机制和生物学功能。一起，这些拟议的研究应显着提高影响机制的基础知识 AHR 调节转录，以实现了解该受体如何发挥作用的长期目标健康和疾病中重要的细胞过程。