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Publication : Dissecting LSD1-Dependent Neuronal Maturation in the Olfactory Epithelium.

First Author  Coleman JH Year  2017
Journal  J Comp Neurol Volume  525
Issue  16 Pages  3391-3413
PubMed ID  28597915 Mgi Jnum  J:252103
Mgi Id  MGI:6102997 Doi  10.1002/cne.24259
Citation  Coleman JH, et al. (2017) Dissecting LSD1-Dependent Neuronal Maturation in the Olfactory Epithelium. J Comp Neurol 525(16):3391-3413
abstractText  Neurons in the olfactory epithelium (OE) each express a single dominant olfactory receptor (OR) allele from among roughly 1,000 different OR genes. While monogenic and monoallelic OR expression has been appreciated for over two decades, regulators of this process are still being described; most recently, epigenetic modifiers have been of high interest as silent OR genes are decorated with transcriptionally repressive trimethylated histone 3 lysine 9 (H3K9me3) whereas active OR genes are decorated with transcriptionally activating trimethylated histone 3 lysine 4 (H3K4me3). The lysine specific demethylase 1 (LSD1) demethylates at both of these lysine residues and has been shown to disrupt neuronal maturation and OR expression in the developing embryonic OE. Despite the growing literature on LSD1 expression in the OE, a complete characterization of the timing of LSD1 expression relative to neuronal maturation and of the function of LSD1 in the adult OE have yet to be reported. To fill this gap, the present study determined that LSD1 (1) is expressed in early dividing cells before OR expression and neuronal maturation and decreases at the time of OR stabilization; (2) colocalizes with the repressor CoREST (also known as RCOR1) and histone deacetylase 2 in these early dividing cells; and (3) is required for neuronal maturation during a distinct time window between activating reserve stem cells (horizontal basal cells) and Neurogenin1 (+) immediate neuronal precursors. Thus, this study clarifies the role of LSD1 in olfactory neuronal maturation.
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