ArticleProceedings of the National Academy of Sciences of the United States of America2013
Rare event of histone demethylation can initiate singular gene expression of olfactory receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain.Cell · 2026Article
- An epigenetic repressor TRIM66 dictates monogenic olfactory receptor expression, neural activity, and olfactory behavior.Nature communications · 2025Article
- Establishment and maintenance of random monoallelic expression.Development (Cambridge, England) · 2024Review
- Epigenetic resetting in the human germ line entails histone modification remodeling.Science advances · 2023Article
- Olfactory receptor choice: a case study for gene regulation in a multi-enhancer system.Current opinion in genetics & development · 2022Review
- Shared Mechanisms for Mutually Exclusive Expression and Antigenic Variation by Protozoan Parasites.Frontiers in cell and developmental biology · 2022Review
- Olfactory receptor coding sequences cause silencing of episomal constructs in multiple cell lines.Molecular and cellular neurosciences · 2021Article
- Stress and odorant receptor feedback during a critical period after hatching regulates olfactory sensory neuron differentiation in Drosophila.PLoS biology · 2021Article
- Modulation of KDM1A with vafidemstat rescues memory deficit and behavioral alterations.PloS one · 2020Article
- Lysine-specific demethylase-1 (LSD1) is compartmentalized at nuclear chromocenters in early post-mitotic cells of the olfactory sensory neuronal lineage.Molecular and cellular neurosciences · 2016Article
- Histone and DNA Modifications as Regulators of Neuronal Development and Function.Cold Spring Harbor perspectives in biology · 2016Review
- Achieving diverse and monoallelic olfactory receptor selection through dual-objective optimization design.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice.Current biology : CB · 2016Article
- Olfactory sensory neurons transiently express multiple olfactory receptors during development.Molecular systems biology · 2015Article
- Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats.Neuroscience · 2015Article
- Chemosensory receptor specificity and regulation.Annual review of neuroscience · 2015Review
- Silver Nanoscale Hexagonal Column Chips for Detecting Cell-free DNA and Circulating Nucleosomes in Cancer Patients.Scientific reports · 2015Article
- Odorant Receptor Gene Choice.ChemoSense · 2015Article
- Monoallelic expression of olfactory receptors.Annual review of cell and developmental biology · 2015Review
- Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons.Cell reports · 2014Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
Mammals sense odors through the gene family of olfactory receptors (ORs). Despite the enormous number of OR genes (∼1,400 in mouse), each olfactory sensory neuron expresses one, and only one, of them. In neurobiology, it remains a long-standing mystery how this singularity can be achieved despite intrinsic stochasticity of gene expression. Recent experiments showed an epigenetic mechanism for maintaining singular OR expression: Once any ORs are activated, their expression inhibits further OR activation by down-regulating a histone demethylase Lsd1 (also known as Aof2 or Kdm1a), an enzyme required for the removal of the repressive histone marker H3K9me3 on OR genes. However, it remains unclear at a quantitative level how singularity can be initiated in the first place. In particular, does a simple activation/feedback scheme suffice to generate singularity? Here we show theoretically that rare events of histone demethylation can indeed produce robust singularity by separating two timescales: slow OR activation by stepwise H3K9me3 demethylation, and fast feedback to turn off Lsd1. Given a typical 1-h response of transcriptional feedback, to achieve the observed extent of singularity (only 2% of neurons express more than one ORs), we predict that OR activation must be as slow as 5–10 d-a timescale compatible with experiments. Our model further suggests H3K9me3-to-H3K9me2 demethylation as an additional rate-limiting step responsible for OR singularity. Our conclusions may be generally applicable to other systems where monoallelic expression is desired, and provide guidelines for the design of a synthetic system of singular expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.