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Electric oscillation and coupling of chromatin regulate chromosome packaging and transcription in eukaryotic cells.

Zhao Y, Zhan Q - Theor Biol Med Model (2012)

Bottom Line: Transcription in eukaryotic cells is efficiently spatially and temporally regulated, but how this genome-wide regulation is achieved at the physical level remains unclear, given the limited transcriptional resources within the nucleus and the sporadic linear arrangements of genes within chromosomes.The COC model, which connects the dots between chromatin epigenetic modification and higher-order nuclear organization, answers many important questions, such as how the CCCTC-binding factor CTCF contributes to higher-order chromatin organization, and the mechanism of sequential transcriptional activation of HOX clusters.Introns of eukaryotic genes have evolved to promote the clustering of transcriptionally co-regulated genes in these sub-nuclear regions.

View Article: PubMed Central - HTML - PubMed

Affiliation: State key laboratory of molecular oncology, Cancer Institute & Hospital of Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. alexanderyz@gmail.com

ABSTRACT
Transcription in eukaryotic cells is efficiently spatially and temporally regulated, but how this genome-wide regulation is achieved at the physical level remains unclear, given the limited transcriptional resources within the nucleus and the sporadic linear arrangements of genes within chromosomes. In this article, we provide a physical model for chromatin cluster formation, based on oscillation synchronization and clustering of different chromatin regions, enabling efficient systemic genome-wide regulation of transcription. We also propose that the electromagnetic field generated by oscillation of chromatin is the driving force for chromosome packing during M phase. We further explore the physical mechanisms for chromatin oscillation cluster (COC) formation, and long-distance chromatin kissing. The COC model, which connects the dots between chromatin epigenetic modification and higher-order nuclear organization, answers many important questions, such as how the CCCTC-binding factor CTCF contributes to higher-order chromatin organization, and the mechanism of sequential transcriptional activation of HOX clusters. In the COC model, long non-coding RNAs function as oscillation clustering adaptors to recruit chromatin modification factors to specific sub-nuclear regions, fine-tuning transcriptional events in the chromatin oscillation clusters. Introns of eukaryotic genes have evolved to promote the clustering of transcriptionally co-regulated genes in these sub-nuclear regions.

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(a) Chromatin regions that share similar natural frequencies are clustered into a proximal region within the cell nucleus. The different colored loops represent different chromatin loops and the blue dots represent chromatin regions functioning as oscillators. These regions may share similar genomic and epigenetic features or bind to certain chromatin-associated protein complexes. They function as chromatin organizers in the nucleus. The green circular region, which contains many of the juxtaposed chromatin oscillators, represents a chromatin oscillation cluster. (b) Schematic illustration of how different chromatin loops are wired through different chromatin oscillation clusters. These COCs further cluster with each other on the basis of average frequencies, forming higher-order chromatin clusters.
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Figure 2: (a) Chromatin regions that share similar natural frequencies are clustered into a proximal region within the cell nucleus. The different colored loops represent different chromatin loops and the blue dots represent chromatin regions functioning as oscillators. These regions may share similar genomic and epigenetic features or bind to certain chromatin-associated protein complexes. They function as chromatin organizers in the nucleus. The green circular region, which contains many of the juxtaposed chromatin oscillators, represents a chromatin oscillation cluster. (b) Schematic illustration of how different chromatin loops are wired through different chromatin oscillation clusters. These COCs further cluster with each other on the basis of average frequencies, forming higher-order chromatin clusters.

Mentions: Certain chromatin regions function as synchronized oscillators, either by coupling of the electromagnetic field generated by longitudinal oscillation of nucleosomes, or by the physical interactions of protein-DNA complexes. The density and positioning of nucleosomes in a chromosome region, the physical properties of histone octamers, as well as the protein complexes binding to the chromatin region, together determine the coupling strength of that region. Through the mechanism described above, these chromatin regions will cluster with each other if they share similar oscillation frequencies, and function as chromatin organizers to shape the higher-order chromatin structures. (Figure 2) from this point of view, we could dissect a segment of chromatin into a number of partially entrained oscillators separated by loosely-coupled chromatin regions in which the structures are less compacted. In addition, it is noteworthy that oscillation clustering would facilitate chromosome rearrangement under physiological and pathological conditions. Thus, specific epigenetic modifications of these chromatin regions would relay specific chromosome rearrangements to upstream signals, resulting in alterations of both sub-nuclear chromatin structures and chromosome structures.


Electric oscillation and coupling of chromatin regulate chromosome packaging and transcription in eukaryotic cells.

Zhao Y, Zhan Q - Theor Biol Med Model (2012)

(a) Chromatin regions that share similar natural frequencies are clustered into a proximal region within the cell nucleus. The different colored loops represent different chromatin loops and the blue dots represent chromatin regions functioning as oscillators. These regions may share similar genomic and epigenetic features or bind to certain chromatin-associated protein complexes. They function as chromatin organizers in the nucleus. The green circular region, which contains many of the juxtaposed chromatin oscillators, represents a chromatin oscillation cluster. (b) Schematic illustration of how different chromatin loops are wired through different chromatin oscillation clusters. These COCs further cluster with each other on the basis of average frequencies, forming higher-order chromatin clusters.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472328&req=5

Figure 2: (a) Chromatin regions that share similar natural frequencies are clustered into a proximal region within the cell nucleus. The different colored loops represent different chromatin loops and the blue dots represent chromatin regions functioning as oscillators. These regions may share similar genomic and epigenetic features or bind to certain chromatin-associated protein complexes. They function as chromatin organizers in the nucleus. The green circular region, which contains many of the juxtaposed chromatin oscillators, represents a chromatin oscillation cluster. (b) Schematic illustration of how different chromatin loops are wired through different chromatin oscillation clusters. These COCs further cluster with each other on the basis of average frequencies, forming higher-order chromatin clusters.
Mentions: Certain chromatin regions function as synchronized oscillators, either by coupling of the electromagnetic field generated by longitudinal oscillation of nucleosomes, or by the physical interactions of protein-DNA complexes. The density and positioning of nucleosomes in a chromosome region, the physical properties of histone octamers, as well as the protein complexes binding to the chromatin region, together determine the coupling strength of that region. Through the mechanism described above, these chromatin regions will cluster with each other if they share similar oscillation frequencies, and function as chromatin organizers to shape the higher-order chromatin structures. (Figure 2) from this point of view, we could dissect a segment of chromatin into a number of partially entrained oscillators separated by loosely-coupled chromatin regions in which the structures are less compacted. In addition, it is noteworthy that oscillation clustering would facilitate chromosome rearrangement under physiological and pathological conditions. Thus, specific epigenetic modifications of these chromatin regions would relay specific chromosome rearrangements to upstream signals, resulting in alterations of both sub-nuclear chromatin structures and chromosome structures.

Bottom Line: Transcription in eukaryotic cells is efficiently spatially and temporally regulated, but how this genome-wide regulation is achieved at the physical level remains unclear, given the limited transcriptional resources within the nucleus and the sporadic linear arrangements of genes within chromosomes.The COC model, which connects the dots between chromatin epigenetic modification and higher-order nuclear organization, answers many important questions, such as how the CCCTC-binding factor CTCF contributes to higher-order chromatin organization, and the mechanism of sequential transcriptional activation of HOX clusters.Introns of eukaryotic genes have evolved to promote the clustering of transcriptionally co-regulated genes in these sub-nuclear regions.

View Article: PubMed Central - HTML - PubMed

Affiliation: State key laboratory of molecular oncology, Cancer Institute & Hospital of Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. alexanderyz@gmail.com

ABSTRACT
Transcription in eukaryotic cells is efficiently spatially and temporally regulated, but how this genome-wide regulation is achieved at the physical level remains unclear, given the limited transcriptional resources within the nucleus and the sporadic linear arrangements of genes within chromosomes. In this article, we provide a physical model for chromatin cluster formation, based on oscillation synchronization and clustering of different chromatin regions, enabling efficient systemic genome-wide regulation of transcription. We also propose that the electromagnetic field generated by oscillation of chromatin is the driving force for chromosome packing during M phase. We further explore the physical mechanisms for chromatin oscillation cluster (COC) formation, and long-distance chromatin kissing. The COC model, which connects the dots between chromatin epigenetic modification and higher-order nuclear organization, answers many important questions, such as how the CCCTC-binding factor CTCF contributes to higher-order chromatin organization, and the mechanism of sequential transcriptional activation of HOX clusters. In the COC model, long non-coding RNAs function as oscillation clustering adaptors to recruit chromatin modification factors to specific sub-nuclear regions, fine-tuning transcriptional events in the chromatin oscillation clusters. Introns of eukaryotic genes have evolved to promote the clustering of transcriptionally co-regulated genes in these sub-nuclear regions.

Show MeSH