Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons
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 cue...
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doaj-99f63647bad24e158816e2f6323738de2020-11-24T21:18:04ZengElsevierCell Reports2211-12472014-11-019388489210.1016/j.celrep.2014.10.001Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory NeuronsDavid B. Lyons0Angeliki Magklara1Tracie Goh2Srihari C. Sampath3Anne Schaefer4Gunnar Schotta5Stavros Lomvardas6Tetrad Program, University of California, San Francisco, San Francisco, CA 94158, USADivision of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 45110 Ioannina, GreeceDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94920, USALaboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USALaboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USAMunich Center for Integrated Protein Science, Adolf-Butenandt-Institute, Ludwig Maximilian University, Schillerstrasse 44, 80336 Munich, GermanyTetrad Program, University of California, San Francisco, San Francisco, CA 94158, USAAn 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.http://www.sciencedirect.com/science/article/pii/S2211124714008419 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David B. Lyons Angeliki Magklara Tracie Goh Srihari C. Sampath Anne Schaefer Gunnar Schotta Stavros Lomvardas |
spellingShingle |
David B. Lyons Angeliki Magklara Tracie Goh Srihari C. Sampath Anne Schaefer Gunnar Schotta Stavros Lomvardas Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons Cell Reports |
author_facet |
David B. Lyons Angeliki Magklara Tracie Goh Srihari C. Sampath Anne Schaefer Gunnar Schotta Stavros Lomvardas |
author_sort |
David B. Lyons |
title |
Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons |
title_short |
Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons |
title_full |
Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons |
title_fullStr |
Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons |
title_full_unstemmed |
Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons |
title_sort |
heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2014-11-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124714008419 |
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