GSE116502
A conserved odor detection pathway via modulation of chromatin and cellular gene expression
Odorants in the environment that can cross the cell membrane are likely important detection targets for a conserved pathway and using one such odorant, diacetyl, we show that the ancient family of histone deacetylase enzymes (HDACs) can act as an atypical odorant detection pathway. Based on our testing we demonstrate that this response meets 6 characteristics of an odor-sensing pathway to odorant exposure: (1) a highly specific response to volatile compounds by altering gene expression, (2) differential modulation of different HDACs, (3) dose-dependent response in vitro, (4) dose-dependent response in vivo, (5) reversible to some degree, and (6) highly conserved across eukaryotes such as invertebrates, vertebrates and plants. We observe that exposure to diacetyl vapors modulates gene expression over a period of days in the Drosophila antenna. The up-regulated genes significantly overlap with genes altered by known histone deacetylase inhibitors administered in the food. In vitro assays with purified human proteins showed that different members of  class I HDACs are differentially inhibited. Moreover exposure to diacetyl increased histone H3K4 acetylation in a human cell line. Organisms spanning multiple taxa can respond to diacetyl volatiles by altering gene expression, presumably in part via inhibition of histone deacetylase proteins causing epigenetic changes. Our finding reveals a highly conserved and slow-acting pathway for responding to odorants beyond the fast-acting neuronal activation via transmembrane receptors, and raises questions about the effects of this odorant detection pathway on physiology and health of organisms. Overall design: Drosophila diacetyl-exposed antenna: RNA-Seq profiles were generated with the Illumina HiSeq2000 platform with biological replicates. Diacetyl-treated antennal samples were compared to control antennal samples from flies exposed to the solvent (paraffin oil, PO) alone. Drosophila diacetyl-recovery antenna: RNA-Seq profiles were generated with the Illumina HiSeq2000 platform with biological replicates. Diacetyl flies were put into recovery for 5days. These antennal samples were compared to control antennal samples exposed to the solvent (paraffin oil, PO) alone throughout the experiment. Drosophila HDACi antenna: RNA-Seq profiles were generated with the Illumina HiSeq2000 platform with biological replicates. HDACi-treated antennal samples were compared to control, untreated antennal samples. Mus musculus lung: RNA-Seq profiles were generated with the Illumina NextSeq200 platform with biological replicates. Diacetyl-treated lung samples were compared to control lung samples from mice exposed to the solvent (PO) alone. Arabidopsis thaliana leaflet: RNA-Seq profiles were generated with the Illumina NextSeq200 platform with biological replicates. Diacetyl-treated leaflet samples were compared to control leaflet samples from plants exposed to the solvent (PO) alone. Mus musculus brain: RNA-Seq profiles were generated with the Illumina NextSeq200 platform with biological replicates. Diacetyl-treated brain samples were compared to control brain samples from mice exposed to the solvent (PO) alone.