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Cell Rep. 2014 Nov 6;9(3):884-92. doi: 10.1016/j.celrep.2014.10.001. Epub 2014 Oct 30.

Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons.

Author information

1
Tetrad Program, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Division of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 45110 Ioannina, Greece.
3
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94920, USA.
4
Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
5
Munich Center for Integrated Protein Science, Adolf-Butenandt-Institute, Ludwig Maximilian University, Schillerstrasse 44, 80336 Munich, Germany.
6
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.

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.

PMID:
25437545
PMCID:
PMC4251488
DOI:
10.1016/j.celrep.2014.10.001
[Indexed for MEDLINE]
Free PMC Article

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