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Your Environment. Your Health.

A CORE TRANSCRIPTION FACTOR COMPLEX OF THE ARYL HYDROCARBON RECEPTOR

Export to Word (http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R21ES032038&format=word)
Principal Investigator: Sutter, Thomas R
Institute Receiving Award University Of Memphis
Location Memphis, TN
Grant Number R21ES032038
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 16 Apr 2021 to 31 Mar 2023
DESCRIPTION (provided by applicant): 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.
Science Code(s)/Area of Science(s) Primary: 05 - Signal Transduction
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications No publications associated with this grant
Program Officer Carol Shreffler
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