# Defining the components of olfactory singular expression

> **NIH NIH R01** · HUNTER COLLEGE · 2024 · $624,349

## Abstract

Abstract
 Monoallelic expression is an unusual form of gene regulation that is often associated with
genes that determine cell-type identity. The olfactory system exhibits an intriguing form of
random monoallelic expression. Each sensory neuron in the mouse nose expresses only one
out of over 2000 odorant receptor (OR) alleles. The current model for OR gene selection
involves the interchromosomal aggregation of distributed enhancers into a single active super-
enhancer, driven by the co-binding of transcription factors Lhx2 and Ebf. This super-enhancer
complex attracts all OR promoters. How this assembly selects a single OR gene promoter for
transcription is unknown. Understanding this process requires a better understanding of how
OR gene promoters function in the context of this super-enhancer complex.
 Like OR enhancers, the promoters contain homeodomain (HD) binding sites for Lhx2 and
Olf1/Ebf (O/E) binding sites for Ebf transcription factors. How these sites act in OR promoters
to engage the choice mechanism is not clear. We propose a set of genetic experiments to
define the role of HD and O/E sites in OR promoter function. To do this we will study targeted
OR transgenes that lie outside of OR clusters, providing a unique tool to study what genetic and
epigenetic features are required for OR expression. Moreover, we propose a combined genetic
and biochemical approach to identify the molecular components of the OR choice mechanism in
the nucleus. Taken together, these approaches seek to elucidate for the first time the molecular
basis for OR monoallelic expression. Our findings will shed light on fundamental mechanisms
that govern gene expression in mammals.

## Key facts

- **NIH application ID:** 10773072
- **Project number:** 5R01DC020764-02
- **Recipient organization:** HUNTER COLLEGE
- **Principal Investigator:** PAUL FEINSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $624,349
- **Award type:** 5
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773072

## Citation

> US National Institutes of Health, RePORTER application 10773072, Defining the components of olfactory singular expression (5R01DC020764-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10773072. Licensed CC0.

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