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Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods.

Shopland LS, Johnson CV, Byron M, McNeil J, Lawrence JB - J. Cell Biol. (2003)

Bottom Line: Certain bands showed extensive contact, often aligning with or encircling an SC-35 domain, whereas others did not.All three gene-rich reverse bands showed this more than the gene-poor Giemsa dark bands, and morphometric analyses demonstrated statistically significant differences.Rather than random reservoirs of splicing factors, or factors accumulated on an individual highly active gene, we propose a model of SC-35 domains as functional centers for a multitude of clustered genes, forming local euchromatic "neighborhoods."

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, University of Massachusetts Medical Center, Worcester, MA 01655, USA.

ABSTRACT
Typically, eukaryotic nuclei contain 10-30 prominent domains (referred to here as SC-35 domains) that are concentrated in mRNA metabolic factors. Here, we show that multiple specific genes cluster around a common SC-35 domain, which contains multiple mRNAs. Nonsyntenic genes are capable of associating with a common domain, but domain "choice" appears random, even for two coordinately expressed genes. Active genes widely separated on different chromosome arms associate with the same domain frequently, assorting randomly into the 3-4 subregions of the chromosome periphery that contact a domain. Most importantly, visualization of six individual chromosome bands showed that large genomic segments ( approximately 5 Mb) have striking differences in organization relative to domains. Certain bands showed extensive contact, often aligning with or encircling an SC-35 domain, whereas others did not. All three gene-rich reverse bands showed this more than the gene-poor Giemsa dark bands, and morphometric analyses demonstrated statistically significant differences. Similarly, late-replicating DNA generally avoids SC-35 domains. These findings suggest a functional rationale for gene clustering in chromosomal bands, which relates to nuclear clustering of genes with SC-35 domains. Rather than random reservoirs of splicing factors, or factors accumulated on an individual highly active gene, we propose a model of SC-35 domains as functional centers for a multitude of clustered genes, forming local euchromatic "neighborhoods."

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Data presented here support model 2 (center) rather than model 1 (left), and are further summarized at far right. (Model 1) mRNA metabolic factors, including SC-35 (green), accumulate on transcripts (yellow) of a single highly active gene (red, top left) or genomic clusters of genes (bottom left). This model requires no structural organization of genes relative to the large concentrations of splicing factors, which merely reflect the distribution of transcripts on different genes. (Model 2) Multiple genes (center top) cluster at the periphery of a single large accumulation of mRNA metabolic factors. R-band DNA (light blue), which is gene rich, is more intimately associated with these SC-35 domains than gene-poor G-band DNA (dark blue, bottom center). (Right) Each chromosome territory (aqua) associates with three or four SC-35 domains, indicating specialized regions at the chromosome territory periphery. These contain domain-associated genes that can even come from different chromosome arms. An SC-35 domain can also associate with genes from different chromosomes. Because domain choice for individual genes is often random, the relative positions of their respective chromosomes also may be highly variable.
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fig6: Data presented here support model 2 (center) rather than model 1 (left), and are further summarized at far right. (Model 1) mRNA metabolic factors, including SC-35 (green), accumulate on transcripts (yellow) of a single highly active gene (red, top left) or genomic clusters of genes (bottom left). This model requires no structural organization of genes relative to the large concentrations of splicing factors, which merely reflect the distribution of transcripts on different genes. (Model 2) Multiple genes (center top) cluster at the periphery of a single large accumulation of mRNA metabolic factors. R-band DNA (light blue), which is gene rich, is more intimately associated with these SC-35 domains than gene-poor G-band DNA (dark blue, bottom center). (Right) Each chromosome territory (aqua) associates with three or four SC-35 domains, indicating specialized regions at the chromosome territory periphery. These contain domain-associated genes that can even come from different chromosome arms. An SC-35 domain can also associate with genes from different chromosomes. Because domain choice for individual genes is often random, the relative positions of their respective chromosomes also may be highly variable.

Mentions: The number of genes associated with a given SC-35 domain may be quite large, indicating a complex organization. The four pairs of specific genes examined here each associate with a common SC-35 domain, with their transcripts intermixing in the domain interior. Although only a limited number of genes in the genome (21/∼30,000) have been surveyed for localization with respect to SC-35, half of these loci are nonrandomly domain associated. The clustering of multiple specific genes and extensions of R-band DNA around the periphery of SC-35 domains is clearly reflective of organization around a structure, rather than of factors simply collected on the transcripts of a highly expressed gene (summarized in Fig. 6). This is consistent with our earlier suggestion that each SC-35 domain corresponds at the ultrastructural level to a cluster of interchromatin granules surrounded by perichromatin fibrils, which represent nascent transcripts of individual genes (Xing et al., 1995). Indeed, the extensive intermingling of two different RNAs within a common SC-35 domain strongly suggests that these are not simply two very close, large perichromatin fibrils.


Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods.

Shopland LS, Johnson CV, Byron M, McNeil J, Lawrence JB - J. Cell Biol. (2003)

Data presented here support model 2 (center) rather than model 1 (left), and are further summarized at far right. (Model 1) mRNA metabolic factors, including SC-35 (green), accumulate on transcripts (yellow) of a single highly active gene (red, top left) or genomic clusters of genes (bottom left). This model requires no structural organization of genes relative to the large concentrations of splicing factors, which merely reflect the distribution of transcripts on different genes. (Model 2) Multiple genes (center top) cluster at the periphery of a single large accumulation of mRNA metabolic factors. R-band DNA (light blue), which is gene rich, is more intimately associated with these SC-35 domains than gene-poor G-band DNA (dark blue, bottom center). (Right) Each chromosome territory (aqua) associates with three or four SC-35 domains, indicating specialized regions at the chromosome territory periphery. These contain domain-associated genes that can even come from different chromosome arms. An SC-35 domain can also associate with genes from different chromosomes. Because domain choice for individual genes is often random, the relative positions of their respective chromosomes also may be highly variable.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2172856&req=5

fig6: Data presented here support model 2 (center) rather than model 1 (left), and are further summarized at far right. (Model 1) mRNA metabolic factors, including SC-35 (green), accumulate on transcripts (yellow) of a single highly active gene (red, top left) or genomic clusters of genes (bottom left). This model requires no structural organization of genes relative to the large concentrations of splicing factors, which merely reflect the distribution of transcripts on different genes. (Model 2) Multiple genes (center top) cluster at the periphery of a single large accumulation of mRNA metabolic factors. R-band DNA (light blue), which is gene rich, is more intimately associated with these SC-35 domains than gene-poor G-band DNA (dark blue, bottom center). (Right) Each chromosome territory (aqua) associates with three or four SC-35 domains, indicating specialized regions at the chromosome territory periphery. These contain domain-associated genes that can even come from different chromosome arms. An SC-35 domain can also associate with genes from different chromosomes. Because domain choice for individual genes is often random, the relative positions of their respective chromosomes also may be highly variable.
Mentions: The number of genes associated with a given SC-35 domain may be quite large, indicating a complex organization. The four pairs of specific genes examined here each associate with a common SC-35 domain, with their transcripts intermixing in the domain interior. Although only a limited number of genes in the genome (21/∼30,000) have been surveyed for localization with respect to SC-35, half of these loci are nonrandomly domain associated. The clustering of multiple specific genes and extensions of R-band DNA around the periphery of SC-35 domains is clearly reflective of organization around a structure, rather than of factors simply collected on the transcripts of a highly expressed gene (summarized in Fig. 6). This is consistent with our earlier suggestion that each SC-35 domain corresponds at the ultrastructural level to a cluster of interchromatin granules surrounded by perichromatin fibrils, which represent nascent transcripts of individual genes (Xing et al., 1995). Indeed, the extensive intermingling of two different RNAs within a common SC-35 domain strongly suggests that these are not simply two very close, large perichromatin fibrils.

Bottom Line: Certain bands showed extensive contact, often aligning with or encircling an SC-35 domain, whereas others did not.All three gene-rich reverse bands showed this more than the gene-poor Giemsa dark bands, and morphometric analyses demonstrated statistically significant differences.Rather than random reservoirs of splicing factors, or factors accumulated on an individual highly active gene, we propose a model of SC-35 domains as functional centers for a multitude of clustered genes, forming local euchromatic "neighborhoods."

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, University of Massachusetts Medical Center, Worcester, MA 01655, USA.

ABSTRACT
Typically, eukaryotic nuclei contain 10-30 prominent domains (referred to here as SC-35 domains) that are concentrated in mRNA metabolic factors. Here, we show that multiple specific genes cluster around a common SC-35 domain, which contains multiple mRNAs. Nonsyntenic genes are capable of associating with a common domain, but domain "choice" appears random, even for two coordinately expressed genes. Active genes widely separated on different chromosome arms associate with the same domain frequently, assorting randomly into the 3-4 subregions of the chromosome periphery that contact a domain. Most importantly, visualization of six individual chromosome bands showed that large genomic segments ( approximately 5 Mb) have striking differences in organization relative to domains. Certain bands showed extensive contact, often aligning with or encircling an SC-35 domain, whereas others did not. All three gene-rich reverse bands showed this more than the gene-poor Giemsa dark bands, and morphometric analyses demonstrated statistically significant differences. Similarly, late-replicating DNA generally avoids SC-35 domains. These findings suggest a functional rationale for gene clustering in chromosomal bands, which relates to nuclear clustering of genes with SC-35 domains. Rather than random reservoirs of splicing factors, or factors accumulated on an individual highly active gene, we propose a model of SC-35 domains as functional centers for a multitude of clustered genes, forming local euchromatic "neighborhoods."

Show MeSH