Molecular study of the epigenome involved in the regulation of olfactory receptor gene expression

Abstract

Chemosensory cells located in the nasal cavity of mammals perform the detection of olfactory stimuli. In these cells, proteins belonging to different GPCR families ('G-protein-coupled-receptors') are expressed in a very peculiar fashion: each sensory cell expresses only one of over a thousand different possible receptors. This phenomenon, known as the "singularity of olfactory receptor gene expression", sits at the basis of the olfactory system logic of operation. However, the molecular underpinnings of this phenomenon have not been elucidated, even though the involvement of epigenetic mechanisms have been postulated as a possible explanation. In this project, this hypothesis will be tested through the analysis of the epigenome in olfactory sensory neurons expressing different receptors and in different stages along the sensory neuron differentiation lineage. We plan to use an unbiased strategy that will result in the global identification of the epigenetic alterations exhibited by cells expressing a given odorant receptor. Genome regions in the genome identified in this way will be further validated by gain and loss-of-function experiments. This study will shed light onto the role played by epigenetic modifications in the development and function of the olfactory system and in the receptor gene choice process in mammals. (AU)