Opposing, spatially-determined epigenetic forces impose restrictions on stochastic olfactory receptor choice
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- Elizaveta V Bashkirova
- Integrated Program in Cellular, Molecular and Biomedical Studies, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University
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- Nell Klimpert
- Department of Neuroscience, Division of Biology and Medicine and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University
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- Kevin Monahan
- Department of Biochemistry and Molecular Biology, Rutgers University
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- Christine E Campbell
- Department of Biochemistry, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences
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- Jason Osinski
- Department of Biochemistry, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences
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- Longzhi Tan
- Department of Bioengineering, Stanford University
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- Ira Schieren
- Zuckerman Mind, Brain, and Behavior Institute, Columbia University
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- Ariel Pourmorady
- Integrated Program in Cellular, Molecular and Biomedical Studies, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University
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- Beka Stecky
- Zuckerman Mind, Brain, and Behavior Institute, Columbia University
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- Gilad Barnea
- Department of Neuroscience, Division of Biology and Medicine and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University
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- Xiaoliang Sunney Xie
- Beijing Innovation Center for Genomics, Peking University
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- Ishmail Abdus-Saboor
- Zuckerman Mind, Brain, and Behavior Institute, Columbia University
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- Benjamin M Shykind
- Prevail Therapeutics- a wholly-owned subsidiary of Eli Lilly and Company
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- Bianca J Marlin
- Zuckerman Mind, Brain, and Behavior Institute, Columbia University
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- Richard M Gronostajski
- Department of Biochemistry, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences
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- Alexander Fleischmann
- Department of Neuroscience, Division of Biology and Medicine and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University
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- Stavros Lomvardas
- Zuckerman Mind, Brain, and Behavior Institute, Columbia University
説明
<jats:p>Olfactory receptor (OR) choice represents an example of genetically hardwired stochasticity, where every olfactory neuron expresses one out of ~2000 OR alleles in the mouse genome in a probabilistic, yet stereotypic fashion. Here, we propose that topographic restrictions in OR expression are established in neuronal progenitors by two opposing forces: polygenic transcription and genomic silencing, both of which are influenced by dorsoventral gradients of transcription factors NFIA, B, and X. Polygenic transcription of OR genes may define spatially constrained OR repertoires, among which one OR allele is selected for singular expression later in development. Heterochromatin assembly and genomic compartmentalization of OR alleles also vary across the axes of the olfactory epithelium and may preferentially eliminate ectopically expressed ORs with more dorsal expression destinations from this ‘privileged’ repertoire. Our experiments identify early transcription as a potential ‘epigenetic’ contributor to future developmental patterning and reveal how two spatially responsive probabilistic processes may act in concert to establish deterministic, precise, and reproducible territories of stochastic gene expression.</jats:p>
収録刊行物
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- eLife
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eLife 12 2023-12-18
eLife Sciences Publications, Ltd