Friday, April 26, 2024
4/26/2024
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.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
