535C Poster - 07. Chromatin, epigenetics and genomics
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Rogelio Nunez Flores; Sachiko Haga-Yamanaka; Christi Ann Scott; Anandasankar Ray

Affiliation: University of California, Riverside

Keywords:
a. chromatin structure; j. epigenetics

Eukaryotes coevolve with microbiomes and respond to their secreted metabolites. However, the response to volatile compounds emitted by microbes is poorly understood. We show that a microbial volatile, diacetyl, and other structurally related odorants, can alter gene expression in eukaryotes at a distance from their emission source. These compounds were found to inhibit human histone-deacetylases (HDACs) leading to increased histone-H3K9 acetylation. Most notable, these compounds inhibit HDAC6, a promising up-regulated target in several neurodegenerative diseases. These epigenetic alterations explain the significant changes in gene expression/ physiological changes seen in Drosophila melanogaster models. In a Drosophila melanogaster transgenic model for Huntington’s disease in the fly eye, exposure to the volatiles slowed progression of neurodegeneration similarly to known orally administered HDAC-inhibitor drugs. When we repeated the exposure study in HDAC6[KO] flies bearing the Huntington’s Disease transgene, we also observed similar neuroprotective effects. Our findings suggest that these changes are caused by a conserved atypical signaling pathway that modulates gene expression via changes in chromatin from a distant chemical source.