Epigenetic regulation of olfactory receptor gene choice. Sarah Perry¹, Choon Kiat Sim², Sana Tharadra¹, Anand Ray¹. 1) Entomology, UC Riverside, Riverside, CA; 2) Department of Genetics, Stanford University, Stanford, CA.

   An olfactory neuron will express a single receptor or receptor pair from amongst a large gene family. It is not fully understood how the olfactory system is able to create and maintain such a complex map. Here we show that epigenetic mechanisms and chromatin structure play a role in receptor selection. We identify a chromatin modifying complex, MMB/dREAM , which is necessary for proper expression of the carbon dioxide receptor genes Gr63a and Gr21a in the antenna. The presence of Myb in the complex is required for normal expression of Gr63a/21a. Other members of the complex, Mip120 and E2F2, prevent aberrant expression of Gr63a in tissues other than the antennae. Loss of either of these members is associated with an increase in activating H3K4me3 histone modifications at the receptor gene locus throughout head tissue. Repressive chromatin is considered to be important for maintaining singular receptor expression in mammals. We find heterochromatic H3K9me2 modifications at olfactory receptor gene loci in the antennae including Gr63a. The histone methyltransferase responsible for these modifications, Su(var)3-9, acts in genetic opposition to myb and influences Gr63a expression. Finally, we show that another set of chromatin modifiers, histone deacetylases (HDACs), also participate in control of receptor choice. Treatment with HDAC inhibitors increases Gr63a expression in adults, potentially through alteration of chromatin structure. Our findings demonstrate a role for the MMB/dREAM complex in receptor gene choice and suggests that chromatin structure and its modifiers play an important role in creating and maintaining singular receptor expression in the olfactory system.