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Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

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Front. Biol.    2014, Vol. 9 Issue (4) : 255-268    https://doi.org/10.1007/s11515-014-1313-3
REVIEW
Gene positioning and genome function
Nidhi VISHNOI,Jie YAO()
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA
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Abstract

The eukaryotic genome is packaged as chromatin within the three-dimensional nuclear space. Decades of cytological studies have revealed that chromosomes and genes are non-randomly localized within the nucleus and such organizations have important roles on genome function. However, several fundamental questions remain to be resolved. For example, what is required for the preferential localization of a gene to a nuclear landmark? What is the mechanism underlying gene repositioning in the nucleus? How does subnuclear gene positioning regulate gene transcription? Recent studies have revealed that several factors such as DNA sequence composition, specific regulatory sequences, epigenetic modifications, chromatin remodelers, post-transcriptional regulators and nuclear architectural proteins can influence chromatin dynamics and gene positioning in a gene-specific manner among organisms from yeast to human. In this review, we discuss some recent findings as well as experimental tools to investigate subnuclear gene positioning and to explore its implications in genome functions.
Keywords nucleus      transcription      gene positioning      epigenetics      nuclear lamina      chromatin     
Corresponding Author(s): Jie YAO   
Issue Date: 11 August 2014
 Cite this article:   
Nidhi VISHNOI,Jie YAO. Gene positioning and genome function[J]. Front. Biol., 2014, 9(4): 255-268.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-014-1313-3
https://academic.hep.com.cn/fib/EN/Y2014/V9/I4/255
Fig.1  Gene positioning and transcriptional status. The cartoon depicts positioning of transgenes or endogenous genes to different subnuclear compartments and their transcriptional status. Genes or transgenes associated with NPCs, Cajal bodies and transcriptional factories are generally active; genes or transgenes associated with the NL or nucleoli are often inactive.
Fig.2  Imaging tools to detect gene positioning. (A) DNA FISH. Adherent cells grown in cover glasses or chamber slides were fixed with formaldehyde, denatured and hybridized with digoxigenin (DIG) or Biotin-labeled DNA probes (red). After incubation with fluorescently-labeled antibodies, FISH signals could be visualized under a fluorescent microscope. (B) lacO/lacI system. The lacO repeats were stably inserted adjacent to a gene of interest. The fluorescently-tagged lacO binding lac repressor (red) was expressed in these cells. Binding of lacI repressor to lacO repeats enabled the visualization of these loci in live cells. (C) m6A tracer technology. The E. coli adenine methyltransferase Dam enzyme was fused with Lamin B1 and expressed in cells. The genomic regions in molecular contact with Lamin B1 were tagged in vivo with adenine-6-methylation (m6A) (red). When m6A-Tracer — a fluorescently-tagged DpnI truncation mutant that binds to Gm6ATC (green) — was expressed in cells, the LADs could be visualized and tracked.
Fig.3  Spatial compartmentalization at the nuclear periphery. Immunofluorescence staining of TAF3 and histone modifications was performed in mouse C2C12 myoblasts. TAF3, H3K4me3, H3K36me3 (green) were all localized away from the nuclear periphery which was labeled by anti-Lamin B (red). The H3K9me3 mark was present at both the nuclear interior and the nuclear periphery. Scale bar: 2 μm.
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