title: Enhancer interaction networks as a means for singular olfactory receptor expression.
abstract: The transcriptional activation of one out of ?2800 olfactory receptor (OR) alleles is a poorly understood process. Here, we identify a plethora of putative OR enhancers and study their in vivo activity in olfactory neurons. Distinguished by an unusual epigenetic signature, candidate OR enhancers are characterized by extensive interchromosomal interactions associated with OR transcription and share a similar pattern of transcription factor footprints. In particular, we establish the role of the transcription factor Bptf as a facilitator of both enhancer interactions and OR transcription. Our observations agree with the model whereby OR transcription occurs in the context of multiple interacting enhancers. Disruption of these interchromosomal interactions results in weak and multigenic OR expression, suggesting that the rare coincidence of numerous enhancers over a stochastically chosen OR may account for the singularity and robustness in OR transcription.
authors.affiliation: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Eirene
authors.initials: E
authors.lastname: Markenscoff-Papadimitriou
authors.affiliation: Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Allen
authors.affiliation: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Colquitt
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Tracie
authors.initials: T
authors.lastname: Goh
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Karl K
authors.initials: KK
authors.lastname: Murphy
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Monahan
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Colleen P
authors.initials: CP
authors.lastname: Mosley
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
authors.affiliation: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: sl682@columbia.edu.
authors.forename: Stavros
authors.initials: S
authors.lastname: Lomvardas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D034961:Antigens, Nuclear / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009698:Nucleoproteins / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; D009698:Nucleoproteins; D018035:Receptors, Odorant; D014157:Transcription Factors; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins