Abstract

Olfactory receptor (OR) genes compose a family of ~1,300 genes that are expressed in a, seemingly, stochastic and monoallelic fashion in the mouse olfactory epithelium. Each olfactory sensory neuron expresses only one OR gene from the whole repertoire and this singularity is essential for the proper wiring and function of the olfactory system. Here, we present preliminary data that a repressive epigenetic modification, trimethylation of lysine 9 of histone H3, may be responsible for the silencing of all the OR alleles that are not expressed in a sensory neuron. We propose experiments that will monitor the spatial and temporal coordinates of this modification in the olfactory epithelium and will reveal the molecular components that orchestrate it. These experiments are essential for understanding the role of this repressive mechanism in OR choice and will provide targets for future genetic analyses of epigenetic silencing in the nose.

Public Health Relevance

This proposal aims to analyze the epigenetic silencing of olfactory receptor genes during the development of the olfactory epithelium. Olfaction is a primal human sense and understanding the epigenetic regulation of olfactory receptor genes will uncover principles for the generation of mammalian neuronal diversity and function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC010273-03
Application #
8073466
Study Section
Special Emphasis Panel (ZDC1-SRB-Q (62))
Program Officer
Sullivan, Susan L
Project Start
2009-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$148,060
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143