This project investigates the actions of two homeodomain transcription factors that help control expression of nearly all of the more than 1,000 mouse odorant receptor genes, expression so finely regulated that each olfactory nerve cell expresses just one allele of one odorant receptor gene. The overarching hypothesis for the project proposes that homeodomain transcription factor stimulation of odorant receptor gene transcription triggers local positive feedback acting through active chromatin modifications while simultaneously enhancing global negative feedback acting through repressive chromatin modifications, competing events capable of explaining the singularity of odorant receptor expression. This project tests whether the transcription factors act directly at promoters and enhancers of odorant receptor genes, and whether these events are associated with selected active chromatin modifications at odorant receptor genes.

Public Health Relevance

Expression of odorant receptors, which are the largest family of mammalian genes, is so specific that each olfactory sensory nerve cell expresses only one allele of one odorant receptor gene. Mechanisms controlling gene expression are broadly interesting given their fundamental involvement in normal development, cancer and genetic susceptibility to diseases and the odorant receptors represent the most extreme and exquisite example of how cells achieve specificity of expression from a large gene family. Though poorly understood, odorant receptor gene expression does appear to depend on two homeodomain transcription factors, whose actions are the focus of this project.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DC013343-01A1
Application #
8701631
Study Section
Special Emphasis Panel (ZRG1-SCS-N (09))
Program Officer
Sullivan, Susan L
Project Start
2014-03-01
Project End
2016-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$225,000
Indirect Cost
$75,000
Name
University of Kentucky
Department
Physiology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506