title: Lysine-specific demethylase-1 (LSD1) is compartmentalized at nuclear chromocenters in early post-mitotic cells of the olfactory sensory neuronal lineage.
abstract: Mammalian olfaction depends on the development of specialized olfactory sensory neurons (OSNs) that each express one odorant receptor (OR) protein from a large family of OR genes encoded in the genome. The lysine-specific demethylase-1 (LSD1) protein removes activating H3K4 or silencing H3K9 methylation marks at gene promoters and is required for proper OR regulation. We show that LSD1 protein exhibits variable organization within nuclei of developing OSNs, and tends to consolidate into a single dominant compartment at the edges of chromocenters within nuclei of early post-mitotic cells of the mouse olfactory epithelium (MOE). Using an immortalized cell line derived from developing olfactory placode, we show that consolidation of LSD1 appears to be cell-cycle regulated, with a peak occurrence in early G1. LSD1 co-compartmentalizes with CoREST, a protein known to collaborate with LSD1 to carry out a variety of chromatin-modifying functions. We show that LSD1 compartments co-localize with 1-3 OR loci at the exclusion of most OR genes, and commonly associate with Lhx2, a transcription factor involved in OR regulation. Together, our data suggests that LSD1 is sequestered into a distinct nuclear space that might restrict a histone-modifying function to a narrow developmental time window and/or range of OR gene targets.
authors.affiliation: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06457, USA. Electronic address: skilinc@wesleyan.edu.
authors.forename: Seda
authors.initials: S
authors.lastname: Kilinc
authors.affiliation: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06457, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Savarino
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Coleman
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Schwob
authors.affiliation: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06457, USA. Electronic address: rlane@wesleyan.edu.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Lane
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D056970:Co-Repressor Proteins; D016193:G1 Phase; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D018035:Receptors, Odorant / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D056970:Co-Repressor Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; C485650:Rcor2 protein, mouse; D018035:Receptors, Odorant; D012097:Repressor Proteins; D056466:Histone Demethylases; C504076:KDM1a protein, mouse
keywords: Chromocenters; Compartmentalization; H3K9 methylation; LSD1/KDM1A; Neurogenin; Olfactory receptor genes; p27(Kip1)