title: Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons.
abstract: An astounding property of the nervous system is its cellular diversity. This diversity, which was initially realized by morphological and electrophysiological differences, is ultimately produced by variations in gene-expression programs. In most cases, these variations are determined by external cues. However, a growing number of neuronal types have been identified in which inductive signals cannot explain the few but decisive transcriptional differences that cause cell diversification. Here, we show that heterochromatic silencing, which we find is governed by histone methyltransferases G9a (KMT1C) and GLP (KMT1D), is essential for stochastic and singular olfactory receptor (OR) expression. Deletion of G9a and GLP dramatically reduces the complexity of the OR transcriptome, resulting in transcriptional domination by a few ORs and loss of singularity in OR expression. Thus, our data suggest that, in addition to its previously known functions, heterochromatin creates an epigenetic platform that affords stochastic, mutually exclusive gene choices and promotes cellular diversity.
authors.affiliation: Tetrad Program, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Lyons
authors.affiliation: Division of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 45110 Ioannina, Greece.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Magklara
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94920, USA.
authors.forename: Tracie
authors.initials: T
authors.lastname: Goh
authors.affiliation: Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Srihari C
authors.initials: SC
authors.lastname: Sampath
authors.affiliation: Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Schaefer
authors.affiliation: Munich Center for Integrated Protein Science, Adolf-Butenandt-Institute, Ludwig Maximilian University, Schillerstrasse 44, 80336 Munich, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schotta
authors.affiliation: Tetrad Program, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94920, USA. Electronic address: sl682@columbia.edu.
authors.forename: Stavros
authors.initials: S
authors.lastname: Lomvardas
mesh_terms: D000818:Animals; D017353:Gene Deletion; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D056466:Histone Demethylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D006657:Histones; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase