Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
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.

Bibliography

Takizawa, T., Gudla, P. R., Guo, L., Lockett, S., & Misteli, T. (2008). Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP. Genes & Development, 22(4), 489–498.

Authors 5
  1. Takumi Takizawa (first)
  2. Prabhakar R. Gudla (additional)
  3. Liying Guo (additional)
  4. Stephan Lockett (additional)
  5. Tom Misteli (additional)
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Dates
Type When
Created 17 years, 6 months ago (Feb. 15, 2008, 2:05 p.m.)
Deposited 3 years, 9 months ago (Nov. 16, 2021, 12:12 p.m.)
Indexed 1 month, 1 week ago (July 16, 2025, 9:20 a.m.)
Issued 17 years, 6 months ago (Feb. 15, 2008)
Published 17 years, 6 months ago (Feb. 15, 2008)
Published Online 17 years, 6 months ago (Feb. 15, 2008)
Published Print 17 years, 6 months ago (Feb. 15, 2008)
Funders 0

None

@article{Takizawa_2008, title={Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP}, volume={22}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1634608}, DOI={10.1101/gad.1634608}, number={4}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Takizawa, Takumi and Gudla, Prabhakar R. and Guo, Liying and Lockett, Stephan and Misteli, Tom}, year={2008}, month=feb, pages={489–498} }