title: Nuclear aggregation of olfactory receptor genes governs their monogenic expression.
abstract: Gene positioning and regulation of nuclear architecture are thought to influence gene expression. Here, we show that, in mouse olfactory neurons, silent olfactory receptor (OR) genes from different chromosomes converge in a small number of heterochromatic foci. These foci are OR exclusive and form in a cell-type-specific and differentiation-dependent manner. The aggregation of OR genes is developmentally synchronous with the downregulation of lamin b receptor (LBR) and can be reversed by ectopic expression of LBR in mature olfactory neurons. LBR-induced reorganization of nuclear architecture and disruption of OR aggregates perturbs the singularity of OR transcription and disrupts the targeting specificity of the olfactory neurons. Our observations propose spatial sequestering of heterochromatinized OR family members as a basis of monogenic and monoallelic gene expression.
authors.affiliation: Program in Biomedical Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: E Josephine
authors.initials: EJ
authors.lastname: Clowney
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: LeGros
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 Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Fiona G
authors.initials: FG
authors.lastname: Clowney
authors.affiliation: Program in Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Eirene C
authors.initials: EC
authors.lastname: Markenskoff-Papadimitriou
authors.affiliation: Department of Physics, University of Jyväskylä, Jyväskylä FI-40014, Finland.
authors.forename: Markko
authors.initials: M
authors.lastname: Myllys
authors.affiliation: Department of Neuroscience, Brown University, Providence, RI 02912, USA.
authors.forename: Gilad
authors.initials: G
authors.lastname: Barnea
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Larabell
authors.affiliation: Program in Biomedical Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Program in Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: stavros.lomvardas@ucsf.edu.
authors.forename: Stavros
authors.initials: S
authors.lastname: Lomvardas
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics*; D014158:Transcription, Genetic; D000097682:Lamin B Receptor
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D018160:Receptors, Cytoplasmic and Nuclear; D018035:Receptors, Odorant; D000097682:Lamin B Receptor; C096188:Cbx1 protein, mouse