Limits...
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.

Show MeSH

Related in: MedlinePlus

(a) The small red arrows indicate the electric oscillations generated between the neighboring histone octamers by excitation of entropic energy within the cell nucleus. The big red arrow represents the electric field generated by the electric oscillation along the 30 nm chromatin fiber. (b-d) Schematic illustration of several orders of oscillation coupling and clustering of EMFs in chromatin fibers, which facilitate the multi-step event of M phase chromosome packaging. The red and orange arrows indicate the multiple orders of EMFs generated during chromosome packaging. (e) The purple arrows indicate the EMFs of compacted M phase chromosome arms; the purple cycles indicate coupling of EMFs. The duplicated chromosome arms hold a juxtaposed position.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3472328&req=5

Figure 1: (a) The small red arrows indicate the electric oscillations generated between the neighboring histone octamers by excitation of entropic energy within the cell nucleus. The big red arrow represents the electric field generated by the electric oscillation along the 30 nm chromatin fiber. (b-d) Schematic illustration of several orders of oscillation coupling and clustering of EMFs in chromatin fibers, which facilitate the multi-step event of M phase chromosome packaging. The red and orange arrows indicate the multiple orders of EMFs generated during chromosome packaging. (e) The purple arrows indicate the EMFs of compacted M phase chromosome arms; the purple cycles indicate coupling of EMFs. The duplicated chromosome arms hold a juxtaposed position.

Mentions: However, the physical mechanisms that regulate the higher-order chromosome packing of metaphase chromosomes have not been fully characterized. Here we present a hypothetical mechanism of chromosome compaction. The 30 nm chromatin fiber is initially formed through electrostatic forces between neighboring nucleosomes. Under intracellular stochastic energy excitation, electric dipolar oscillation would be generated between such nucleosomes. After synchronization and coupling of the oscillations, regulated oscillations are generated along the 30 nm chromatin fiber, and the oscillation coupling process further compacts the 30 nm fiber [12-14]. The compaction facilitates further packing of this fiber into the 300 nm chromatin fiber; the electric field bends according to the physical curvature of the compacting 30 nm fiber, generating an oscillating electromagnetic field that goes through the 300 nm fiber. The second round of oscillation synchronization and coupling results in the formation of the 250 nm chromosome fiber and facilitates its packing into the 700 nm chromosome fiber. The bending of the electromagnetic field of the 250 nm fiber around the curvature of the 700 nm fiber generates a higher-order electric field that goes through 700 nm fiber; thereafter, oscillation coupling further compacts the 700 nm fiber into chromosome arms [15,16]. We speculate that the source of the energy for the electric dipolar oscillation between neighboring nucleosomes in a chromatin fiber is the variety of intracellular entropic forces, and the direction of the electric oscillation primarily depends on the zigzag arrangement of neighboring nucleosomes along the 30 nm fiber (Figure 1).


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

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

(a) The small red arrows indicate the electric oscillations generated between the neighboring histone octamers by excitation of entropic energy within the cell nucleus. The big red arrow represents the electric field generated by the electric oscillation along the 30 nm chromatin fiber. (b-d) Schematic illustration of several orders of oscillation coupling and clustering of EMFs in chromatin fibers, which facilitate the multi-step event of M phase chromosome packaging. The red and orange arrows indicate the multiple orders of EMFs generated during chromosome packaging. (e) The purple arrows indicate the EMFs of compacted M phase chromosome arms; the purple cycles indicate coupling of EMFs. The duplicated chromosome arms hold a juxtaposed position.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: (a) The small red arrows indicate the electric oscillations generated between the neighboring histone octamers by excitation of entropic energy within the cell nucleus. The big red arrow represents the electric field generated by the electric oscillation along the 30 nm chromatin fiber. (b-d) Schematic illustration of several orders of oscillation coupling and clustering of EMFs in chromatin fibers, which facilitate the multi-step event of M phase chromosome packaging. The red and orange arrows indicate the multiple orders of EMFs generated during chromosome packaging. (e) The purple arrows indicate the EMFs of compacted M phase chromosome arms; the purple cycles indicate coupling of EMFs. The duplicated chromosome arms hold a juxtaposed position.
Mentions: However, the physical mechanisms that regulate the higher-order chromosome packing of metaphase chromosomes have not been fully characterized. Here we present a hypothetical mechanism of chromosome compaction. The 30 nm chromatin fiber is initially formed through electrostatic forces between neighboring nucleosomes. Under intracellular stochastic energy excitation, electric dipolar oscillation would be generated between such nucleosomes. After synchronization and coupling of the oscillations, regulated oscillations are generated along the 30 nm chromatin fiber, and the oscillation coupling process further compacts the 30 nm fiber [12-14]. The compaction facilitates further packing of this fiber into the 300 nm chromatin fiber; the electric field bends according to the physical curvature of the compacting 30 nm fiber, generating an oscillating electromagnetic field that goes through the 300 nm fiber. The second round of oscillation synchronization and coupling results in the formation of the 250 nm chromosome fiber and facilitates its packing into the 700 nm chromosome fiber. The bending of the electromagnetic field of the 250 nm fiber around the curvature of the 700 nm fiber generates a higher-order electric field that goes through 700 nm fiber; thereafter, oscillation coupling further compacts the 700 nm fiber into chromosome arms [15,16]. We speculate that the source of the energy for the electric dipolar oscillation between neighboring nucleosomes in a chromatin fiber is the variety of intracellular entropic forces, and the direction of the electric oscillation primarily depends on the zigzag arrangement of neighboring nucleosomes along the 30 nm fiber (Figure 1).

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
Related in: MedlinePlus