First Author | Lyons DB | Year | 2013 |
Journal | Cell | Volume | 154 |
Issue | 2 | Pages | 325-36 |
PubMed ID | 23870122 | Mgi Jnum | J:200085 |
Mgi Id | MGI:5506971 | Doi | 10.1016/j.cell.2013.06.039 |
Citation | Lyons DB, et al. (2013) An epigenetic trap stabilizes singular olfactory receptor expression. Cell 154(2):325-36 |
abstractText | The molecular mechanisms regulating olfactory receptor (OR) expression in the mammalian nose are not yet understood. Here, we identify the transient expression of histone demethylase LSD1 and the OR-dependent expression of adenylyl cyclase 3 (Adcy3) as requirements for initiation and stabilization of OR expression. As a transcriptional coactivator, LSD1 is necessary for desilencing and initiating OR transcription, but as a transcriptional corepressor, it is incompatible with maintenance of OR expression, and its downregulation is imperative for stable OR choice. Adcy3, a sensor of OR expression and a transmitter of an OR-elicited feedback, mediates the downregulation of LSD1 and promotes the differentiation of olfactory sensory neurons (OSNs). This novel, three-node signaling cascade locks the epigenetic state of the chosen OR, stabilizes its singular expression, and prevents the transcriptional activation of additional OR alleles for the life of the neuron. |