title: Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP.
abstract: Chromosomes and genes are nonrandomly arranged within the mammalian cell nucleus. However, the functional significance of nuclear positioning in gene expression is unclear. Here we directly probed the relationship between nuclear positioning and gene activity by comparing the location of the active and inactive copies of a monoallelically expressed gene in single cell nuclei. We demonstrate that the astrocyte-specific marker GFAP (glial fibrillary acidic protein) is monoallelically expressed in cortical astrocytes. Selection of the active allele occurs in a stochastic manner and is generally maintained through cell division. Taking advantage of the monoallelic expression of GFAP, we show that the functionally distinct alleles occupy differential radial positions within the cell nucleus and differentially associate with intranuclear compartments. In addition, coordinately regulated astrocyte-specific genes on distinct chromosomes spatially associate in their inactive state and dissociate upon activation. These results provide direct evidence for function-related differential positioning of individual gene alleles within the interphase nucleus.
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Takumi
authors.initials: T
authors.lastname: Takizawa
authors.forename: Prabhakar R
authors.initials: PR
authors.lastname: Gudla
authors.forename: Liying
authors.initials: L
authors.lastname: Guo
authors.forename: Stephan
authors.initials: S
authors.lastname: Lockett
authors.forename: Tom
authors.initials: T
authors.lastname: Misteli
mesh_terms: D000483:Alleles; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000502:physiology*; D015151:Immunoblotting; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger