RRC ID 5379
Author Takizawa T, Gudla PR, Guo L, Lockett S, Misteli T.
Title Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP.
Journal Genes Dev.
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.
Volume 22(4)
Pages 489-98
Published 2008-2-15
DOI 10.1101/gad.1634608
PII 22/4/489
PMID 18281462
PMC PMC2238670
MeSH Alleles* Animals Astrocytes / physiology* Biomarkers / metabolism* Cell Differentiation* Cell Nucleus / genetics* Cell Nucleus / metabolism Cell Nucleus / ultrastructure Glial Fibrillary Acidic Protein / genetics Glial Fibrillary Acidic Protein / physiology* Immunoblotting In Situ Hybridization, Fluorescence Mice RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction
IF 8.99
Times Cited 87