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：
10218975
负责人：
THOMAS R SUTTER
金额：
$ 17.94万
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 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10218975
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.

该项目的目的是研究AHR的核心转录因子（TF）复合物（Aryl 通过分析高含量染色质免疫沉淀-DNA，我们发现了碳氢化合物受体） DNA元素百科全书（编码）项目的序列（CHIP-SEQ），一个公共研究项目确定人类基因组中的所有功能元素。在这个项目中，我们将验证这个复合物，确定它的物理组织和功能，并评估该复合物是否在细胞之间保存以及物种。 AHR最著名的是配体激活转录因子（TF），在二恶英样化合物（DLC）的毒性，包括癌症，先天缺陷和免疫抑制，以及调节诸如细胞色素P450家族的酶1个可以激活procarcinogens的成员。此外，最近的研究表明，AHR在调节细胞体内平衡中的关键作用，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护。目标2。阐明AHR核心TF复合物的调节机制和生物学功能。一起，这些提出的研究应明显提高对影响机制的基本知识 AHR调节的转录朝着理解该受体如何有助于的长期目标健康和疾病中的重要细胞过程。