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Comment
. 2008 Sep 22;182(6):1035-8.
doi: 10.1083/jcb.200808121.

Gene associations: true romance or chance meeting in a nuclear neighborhood?

Jeanne B Lawrence  1 , Christine M Clemson
Affiliations
Comment

Gene associations: true romance or chance meeting in a nuclear neighborhood? (V体育官网入口)

Jeanne B Lawrence et al. J Cell Biol. .

Abstract

Many recent studies have raised interest in the nuclear associations of coregulated genes from different chromosomes, often evoking interpretations of gene-gene interactions, communication, and even "romance. " However, in some cases, the associations may be indirect and infrequent and may reflect the segregation of active and inactive genes into different nuclear compartments. The study by Brown et al VSports手机版. (see p. 1083 of this issue) reports that the apparent association of erythroid genes is not a direct interaction nor colocalization to one tiny transcription factory but arises as a result of the known clustering of many active genes with larger splicing factor-rich speckles (a. k. a. , SC35-defined domains). This clustering appears largely stochastic but is impacted by the chromosomal neighborhood of the gene as well as its transcriptional status. The study adds a new twist by examining the same gene in a foreign chromosomal context, providing evidence that this impacts a gene's propensity to form gene-domain (or apparent gene-gene) associations within nuclei. .

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Figures

Figure 1.
Figure 1.
Localization of active genes or chromosome regions with splicing factor (SC35)–rich domains impacts their overall nuclear organization. (A) COL1A1 and COL1A2 genes on separate chromosomes can associate with a common SC35 domain, increasing their proximity to each other. Human diploid fibroblasts hybridized with genomic probes to COL1A1 (red) and COL1A2 (green) and stained for SC35 (blue). One allele of each gene is positioned at the periphery of the same SC35 domain in the cell shown. Although this brings these loci closer, they remain separate. (B) COL1A1 and COL1A2 RNA foci can be completely coincident within an SC35 domain. Transcripts from the COL1A1 (green) and COL1A2 (red) genes enter the SC35 domain and can completely overlap within this common SC35 domain (blue). Although RNA foci completely overlap, genes remain separate. Overlap between the three colors appears white. (C–E) Clustering of genes in bands on chromosomes may relate to their clustering with nuclear substructures. (C) The G-band probe for 3p14 (red) shows two relatively compact bands minimally contacting SC35 domains (green). (D) The probe for a similarly sized segment of R-band 17q21 DNA (red) shows two signals that are much more highly extended and show more regions intimately contacting SC35 domains. (E) Model for the differential organization of R- and G-band DNA with respect to SC35-rich domains and euchromatic neighborhoods. Multiple genes cluster at the periphery of a single, very large accumulation (domain) of mRNA metabolic factors, forming a more euchromatic neighborhood around the domain. R-band DNA (light blue), which is somewhat more gene rich, is more intimately associated with these SC35 domains than more tightly packaged G-band DNA (dark blue). (right) Ideogram and actual appearance of cytogenetic bands and sub-bands are shown for chromosome 17. This figure is modified from Shopland et al. (2003). Bar, 5 μm.
Figure 2.
Figure 2.
Alternative explanations for interchromosomal gene associations seen by 3C analysis. (A) A direct molecular interaction of two gene loci occurs such that the formaldehyde cross-links form (gray) via their chromatin proteins. (B) Two DNA segments that localize to a common nuclear structure will infrequently be near enough to one another to be cross-linked via their chromatin proteins (left) or to be indirectly connected via mutual cross-links to the larger aggregation of splicing factors or other protein accumulations (right). The latter may involve multiple cross-links, but subsequent ligation and PCR amplification would occur in the absence of a direct in vivo molecular interaction.
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References

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