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The yin and yang of chromatin spatial organization.

Cope NF, Fraser P, Eskiw CH - Genome Biol. (2010)

Bottom Line: Spatial organization of the genome is non-random.Preferential chromatin interactions, both in cis and in trans and between transcriptionally active and silent regions, influence organization.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Chromatin and Gene Expression, The Babraham Institute, Babraham Research Campus, Cambridge, UK.

ABSTRACT
Spatial organization of the genome is non-random. Preferential chromatin interactions, both in cis and in trans and between transcriptionally active and silent regions, influence organization.

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Colocalization of like-regulated genes and specialized transcription factories. (a) Quadruple-label RNA immuno-FISH of three genes that are being transcribed and their association with RNAPII transcription factories. RNAPII staining is shown on the left and an overlay of the RNAPII staining showing the contributions of the genes is on the right. The side panels show the enlarged images of colocalizing FISH signals, showing that transcription factories can simultaneously transcribe at least three genes, located on different chromosomes. (b) Immunofluorescence detection of Klf1 (red) and RNAPII transcription factories (green), showing the selective and specialized nature of transcription factories. (c) Triple-label RNA immuno-FISH for Hbb and Epb4.9, showing association of these genes at Klf1 foci. All images show definitive erythroid cells and the scale bar in each panel represents 2 μm. Reproduced, with permission, from [24].
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Figure 3: Colocalization of like-regulated genes and specialized transcription factories. (a) Quadruple-label RNA immuno-FISH of three genes that are being transcribed and their association with RNAPII transcription factories. RNAPII staining is shown on the left and an overlay of the RNAPII staining showing the contributions of the genes is on the right. The side panels show the enlarged images of colocalizing FISH signals, showing that transcription factories can simultaneously transcribe at least three genes, located on different chromosomes. (b) Immunofluorescence detection of Klf1 (red) and RNAPII transcription factories (green), showing the selective and specialized nature of transcription factories. (c) Triple-label RNA immuno-FISH for Hbb and Epb4.9, showing association of these genes at Klf1 foci. All images show definitive erythroid cells and the scale bar in each panel represents 2 μm. Reproduced, with permission, from [24].

Mentions: RNA polymerase II (RNAPII)-transcribed genes, which represent the majority of protein coding genes, also engage in long-range transcription-dependent associations [22,23]. Transcriptionally active genes, such as those genes involved with globin synthesis and regulation, have been shown to colocalize with shared RNAPII foci [22,24] (Figure 3a). Co-regulated genes in cis and in trans share RNAPII foci with each other at higher frequencies than they do with other transcribed genes, suggesting the presence of large-scale transcription networks [24]. These preferential interactions occur at nuclear subcompartments containing high local concentrations of hyperphosphorylated RNAPII, called transcription factories. Described as protein rich structures of about 10 MDa with an average diameter of about 87 nm, transcription factories contain multiple active RNAPII complexes at one time [25-27]. Gene interactions at transcription factories rely on active transcription: heat-shock treatment, which blocks initiation and elongation, resulted in release of genes from factories and disruption of their long-range associations [23]. Treatment with 5,6-dichloro- β-D-ribofuranosylbenzimidazole (DRB), which interferes with phosphorylation of the carboxy-terminal domain of RNAPII and thus inhibits transcriptional elongation but not initiation, did not affect the frequency of gene co-associations [23]. Transcription initiation is therefore critical for the long-range association of genes that are being transcribed. Transcription factories remained after heat shock, consistent with previous results suggesting that factories are meta-stable structures [28]. These findings indicate that the structure and function of transcription factories are fundamental to long-range interactions between genes being transcribed.


The yin and yang of chromatin spatial organization.

Cope NF, Fraser P, Eskiw CH - Genome Biol. (2010)

Colocalization of like-regulated genes and specialized transcription factories. (a) Quadruple-label RNA immuno-FISH of three genes that are being transcribed and their association with RNAPII transcription factories. RNAPII staining is shown on the left and an overlay of the RNAPII staining showing the contributions of the genes is on the right. The side panels show the enlarged images of colocalizing FISH signals, showing that transcription factories can simultaneously transcribe at least three genes, located on different chromosomes. (b) Immunofluorescence detection of Klf1 (red) and RNAPII transcription factories (green), showing the selective and specialized nature of transcription factories. (c) Triple-label RNA immuno-FISH for Hbb and Epb4.9, showing association of these genes at Klf1 foci. All images show definitive erythroid cells and the scale bar in each panel represents 2 μm. Reproduced, with permission, from [24].
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Related In: Results  -  Collection

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Figure 3: Colocalization of like-regulated genes and specialized transcription factories. (a) Quadruple-label RNA immuno-FISH of three genes that are being transcribed and their association with RNAPII transcription factories. RNAPII staining is shown on the left and an overlay of the RNAPII staining showing the contributions of the genes is on the right. The side panels show the enlarged images of colocalizing FISH signals, showing that transcription factories can simultaneously transcribe at least three genes, located on different chromosomes. (b) Immunofluorescence detection of Klf1 (red) and RNAPII transcription factories (green), showing the selective and specialized nature of transcription factories. (c) Triple-label RNA immuno-FISH for Hbb and Epb4.9, showing association of these genes at Klf1 foci. All images show definitive erythroid cells and the scale bar in each panel represents 2 μm. Reproduced, with permission, from [24].
Mentions: RNA polymerase II (RNAPII)-transcribed genes, which represent the majority of protein coding genes, also engage in long-range transcription-dependent associations [22,23]. Transcriptionally active genes, such as those genes involved with globin synthesis and regulation, have been shown to colocalize with shared RNAPII foci [22,24] (Figure 3a). Co-regulated genes in cis and in trans share RNAPII foci with each other at higher frequencies than they do with other transcribed genes, suggesting the presence of large-scale transcription networks [24]. These preferential interactions occur at nuclear subcompartments containing high local concentrations of hyperphosphorylated RNAPII, called transcription factories. Described as protein rich structures of about 10 MDa with an average diameter of about 87 nm, transcription factories contain multiple active RNAPII complexes at one time [25-27]. Gene interactions at transcription factories rely on active transcription: heat-shock treatment, which blocks initiation and elongation, resulted in release of genes from factories and disruption of their long-range associations [23]. Treatment with 5,6-dichloro- β-D-ribofuranosylbenzimidazole (DRB), which interferes with phosphorylation of the carboxy-terminal domain of RNAPII and thus inhibits transcriptional elongation but not initiation, did not affect the frequency of gene co-associations [23]. Transcription initiation is therefore critical for the long-range association of genes that are being transcribed. Transcription factories remained after heat shock, consistent with previous results suggesting that factories are meta-stable structures [28]. These findings indicate that the structure and function of transcription factories are fundamental to long-range interactions between genes being transcribed.

Bottom Line: Spatial organization of the genome is non-random.Preferential chromatin interactions, both in cis and in trans and between transcriptionally active and silent regions, influence organization.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Chromatin and Gene Expression, The Babraham Institute, Babraham Research Campus, Cambridge, UK.

ABSTRACT
Spatial organization of the genome is non-random. Preferential chromatin interactions, both in cis and in trans and between transcriptionally active and silent regions, influence organization.

Show MeSH