An epigenetic repressor TRIM66 dictates monogenic olfactory receptor expression, neural activity, and olfactory
Hongqiang Bao1,2, Rong Liu1,2, Yalei Kong1,2
1Department of Otolaryngology, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature Communications
|December 12, 2025
Summary
Researchers identified TRIM66 as a key repressor in olfactory receptor gene choice. Deleting Trim66 in olfactory sensory neurons (OSNs) disrupts the silencing of olfactory receptor genes, impacting olfactory processing and behavior.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Olfactory receptor (OR) gene choice is a complex process of monogenic and monoallelic expression.
- Immature olfactory sensory neurons (OSNs) express multiple OR genes, silencing all but one during maturation.
- The molecular mechanisms and repressors controlling this silencing remain largely unknown.
Purpose of the Study:
- To identify the molecular repressors responsible for silencing extra olfactory receptor genes.
- To elucidate the mechanism by which olfactory receptor gene expression transitions from polygenic to monogenic.
- To investigate the functional consequences of impaired olfactory receptor gene silencing.
Main Methods:
- Utilized genetic deletion of Trim66 in mouse models.
- Analyzed gene expression in single mature olfactory sensory neurons (OSNs).
- Investigated the molecular interactions of TRIM66 with olfactory receptor enhancers.
Main Results:
- TRIM66 was identified as a crucial repressor of olfactory receptor gene expression.
- Deletion of Trim66 resulted in the retention of multiple OR genes in mature OSNs.
- TRIM66 binds to and represses olfactory receptor enhancers, silencing extra OR genes.
- Trim66 deletion led to significant defects in olfactory information processing and innate behaviors.
Conclusions:
- TRIM66 is a key molecular player in the transition from polygenic to monogenic olfactory receptor expression.
- TRIM66-mediated repression is essential for proper olfactory sensory neuron function and behavior.
- This study identifies the missing link in understanding olfactory gene choice regulation.
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