Integrated Program in Cellular, Molecular and Biomedical Studies, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, New York, United States; Zuckerman Mind, Brain, and Behavior Institute, Columbia University, New York, United States
Department of Neuroscience, Division of Biology and Medicine and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, United States
Kevin Monahan
Department of Biochemistry and Molecular Biology, Rutgers University, Newark, United States
Christine E Campbell
Department of Biochemistry, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, United States; Genetics, Genomics, and Bioinformatics Graduate Program, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, United States
Jason Osinski
Department of Biochemistry, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, United States; Genetics, Genomics, and Bioinformatics Graduate Program, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, United States
Longzhi Tan
Department of Bioengineering, Stanford University, Stanford, United States
Ira Schieren
Zuckerman Mind, Brain, and Behavior Institute, Columbia University, New York, United States
Ariel Pourmorady
Integrated Program in Cellular, Molecular and Biomedical Studies, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, New York, United States; Zuckerman Mind, Brain, and Behavior Institute, Columbia University, New York, United States
Beka Stecky
Zuckerman Mind, Brain, and Behavior Institute, Columbia University, New York, United States
Department of Neuroscience, Division of Biology and Medicine and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, United States
Xiaoliang Sunney Xie
Beijing Innovation Center for Genomics, Peking University, Beijing, China; Biomedical Pioneering Innovation Center, Peking University, Beijing, China
Zuckerman Mind, Brain, and Behavior Institute, Columbia University, New York, United States
Richard M Gronostajski
Department of Biochemistry, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, United States; Genetics, Genomics, and Bioinformatics Graduate Program, University at Buffalo and New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, United States
Department of Neuroscience, Division of Biology and Medicine and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, United States
Zuckerman Mind, Brain, and Behavior Institute, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, New York, United States
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.
