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

In this paper is viewed that DNA conformation and transcription is organised by electromagnetic fields.

" 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."

Nuclear chromatin is clustered and in a fractal globule form. The authors suggest a physical model of synchronization and clustering of pulse-coupled oscillators in the chromatin organization.

In this view clusters are formed among oscillators with similar frequencies, chromatin organization is viewed as differential clustering of oscillating chromatin regions.

" The coupling strengths of chromatin regions are determined by physical interactions among chromatin-associated proteins, the electromagnetic fields around the oscillating chromosomal regions, and the hydrogen and other bonds linking different chromatin regions within the same chromosome. The natural frequency of an oscillating chromatin region is determined by the physical properties of DNA-protein complexes in that region, which can be changed by its epigenetic state and the protein factors associated with it."

So the chromosome compaction regulation is viewed in terms of multiple orders of partial entrainment and clustering events of oscillating chromatin regions.

" Primary clustering of chromosomal regions forms oscillating clusters with average frequencies that become oscillators for a higher order of synchronization and clustering [6]. During M phase, when chromatin regions are compacted into chromosomes, each chromosome can be viewed as a synchronized oscillating cluster with one average frequency, which is the physical basis of the electromagnetic field around that chromosome."

The authors then make a review of some experimental studies of DNA properties with a possible relation to electromagnetic fields, and point out that they can be oriented, aligned and translated by an oscillating electrical force, that it has discovered permanent dipole moments in some dinucleosomes and a linker DNA making zigzags back and forth between two stacks of nucleosome core, etc..

And propose a physical mechanism that regulate the higher order 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."

It can explain the losely-juxtaposed configuration of duplicated chromosomes during M phase; as homologous chromosomal regions comprise synchronized chromosomal oscillation clusters with identical natural frequencies, they tend to cluster together.

They also propose that the oscillation clustering of chromatin regions by EMF brings distant chromatin regions into closely juxtaposed positions, and the oscillation cluster would be further stabilized by protein complexes.

Also they explain the role of chromatin oscillation clusters (COC) in transcriptional regulation.

" For example, sequential transcriptional activation of the HOX gene clusters can be viewed as a sequential uncoupling event of different HOX transcriptional loops within COCs."

And that COC formation increases the epigenetic stability. And go into details of the role of long non-coding RNA in this model.

" Chambeyron et al. suggest that higher-order chromatin structures regulate the expression of the HOX cluster at several levels, including locus-wide changes in chromatin structure and the temporal programming of expression of different genes [23]. Many large intergenic RNAs (Linc RNAs) genes are located within HOX gene clusters, some of which have already been well studied [36,37]. These Linc RNAs are transcribed following the initial transcription onset signal, which is also spatially and temporally regulated. After transcription, these Linc RNAs are clustered autonomously in a COC on the basis of their natural frequencies and the local coupling strengths, which are determined by specific chromatin-associated proteins and the spatial relationship between the COC and the Linc RNAs. Long non-coding RNAs functioning as oscillation adaptors for transcription factors have two advantages. First, they function as scaffolds that can recruit multiple transcription factors and chromosome modifiers to specific genome loci to allow specific epigenetic modification. Secondly, the physical properties of RNA-protein complexes are more likely to have similar natural frequencies with COC than individual proteins, which is critical for transcription factor trafficking in the nucleus."

Last modified on 15-Mar-16

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