QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Takizawa, T. Articles by Misteli, T. Search for Related Content PubMed PubMed Citation Articles by Takizawa, T. Articles by Misteli, T. Social Bookmarking                   What's this?

Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP

¹ National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; ² National Cancer Institute/Science Applications International Corporation-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA; ³ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

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.

[Keywords: Monoallelic expression; spatial gene positioning; nuclear architecture; astrocyte]]

Received May 15, 2007; revised version accepted December 10, 2007.

E-MAIL mistelit{at}mail.nih.gov; FAX (301) 496-4951.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1634608

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?