Characterization of Lysine‐specific Demethylase 1 (LSD1) As a Potential Olfactory Receptor Regulator

Mouse olfactory sensory neurons (OSNs) express a variety of over 1000 odorant receptor (OR) genes located throughout the genome. Previous studies have shown that each OSN expresses only one OR gene out of the >;1000 possible genes and that the expressed locus lacks an H3K9 trimethylation mark. Lysine specific demethylase 1 (LSD1) is a candidate demethylase that may play a role in the epigenetic pathway of OR gene regulation. Preliminary immunofluorescence experiments have shown that LSD1 displays three phenotypes throughout the cell cycle. LSD1 exhibits a broad, diffuse nuclear staining or a highly localized, punctate nuclear expression pattern. Some punctate nuclei exhibit one distinct compartment of LSD1. Cell synchronization experiments show a significantly higher incidence of punctate LSD1 during G2/M phase and a higher frequency of the distinct LSD1 phenotype during telophase. One possible model suggests that all OR loci are initially silenced by trimethylation and that distinct signals represent active LSD1 complexes which derepress a gene locus for future expression. DNA immuno‐FISH experiments show that active OR gene clusters co‐localize with LSD1 distinct and punctate signals within the nucleus of cycling OP6 cells occasionally, while the control, actin, does not co‐localize with LSD1 in cycling cells. Co‐localization would suggest possible LSD1 and OR gene interaction, in which LSD1 may function in the derepression of the expressed OR locus.