Company of mitotic chromosomes (magenta) and spindle microtubules (green) at an early phase of cell department. Chromatin compaction controlled by histone acetylation will avoid the perforation of the chromosomes by microtubules.
How the genome is packed into chromosomes that can be faithfully moved during cellular division.
Researchers discovered a molecular system that confers special physical residential or commercial properties to chromosomes in dividing human cells to enable their devoted transportation to the children. The research group revealed how a chemical modification develops a sharp surface limit on chromosomes, thus enabling them to withstand perforation by microtubules of the spindle apparatus. The scientists are from the Gerlich Group at IMBA– Institute of Molecular Biotechnology of the Austrian Academy of Sciences, and their findings are released today (August 3, 2022) in the journal Nature.
The new findings by the Gerlich Research Group at IMBA– Institute of Molecular Biotechnology of the Austrian Academy of Sciences– shed light on how mitotic chromosomes withstand the continuous pressing and pulling forces produced by the microtubules. “Amidst this complex system, the distinct physical properties are conferred to the chromosomes by changing the levels of histone acetylation, a chemical modification within the chromatin fiber,” states IMBA Group Leader Daniel Gerlich.
Prior research study had demonstrated that, in dividing cells, the chromatin fibers are folded into loops by a large protein complex called condensin. The role of condensin alone might not discuss why chromosomes appear as thick bodies with a sharp surface rather than a loose structure looking like a bottlebrush.
The researchers differed the levels of condensin and histone acetylation to study their accurate impacts. Eliminating condensin interrupted the extended shape of chromosomes in dividing cells and reduced their resistance to pulling forces however did not impact their level of compaction. Integrating condensin deficiency with a treatment that increases the levels of histone acetylation triggered huge chromatin decompaction in dividing cells, and perforation of chromosomes by microtubules.
The team hypothesized that chromatin is organized as an inflamed gel throughout the majority of the cell cycle (when it is fairly highly acetylated) and that this gel compacts to an insoluble kind during cellular division when the acetylation levels worldwide decrease. They then developed an assay to probe the solubility of chromatin by fragmenting mitotic chromosomes into small pieces. The pieces of mitotic chromosomes formed beads of liquid chromatin, however when the acetylation level was increased, the chromatin pieces dissolved in the cytoplasm. These observations support a design where an international reduction of chromatin acetylation during mitosis establishes an immiscible chromatin gel with a sharp stage limit, supplying a physical basis for resistance against microtubule perforation.
With more experiments including pure chromatin that was reconstituted in vitro, and by probing chromatin access by different soluble macromolecules, the scientists discovered that immiscible chromatin forms a structure dense in unfavorable charge that excludes adversely charged macromolecules and microtubules.
” Our study demonstrates how DNA looping by the condensin complex cooperates with a chromatin phase separation procedure to construct mitotic chromosomes that resist both pulling and pressing forces put in by the spindle. The deacetylation of histones throughout cell department for this reason provides unique physical homes to chromosomes that are required for their faithful partition,” concludes Daniel Gerlich.
Reference: “A mitotic chromatin phase transition avoids perforation by microtubules” 3 August 2022, Nature.DOI: 10.1038/ s41586-022-05027-y.
Funding: Austrian Science Fund, Vienna Science and Technology Fund, Vienna Science and Technology Fund, Howard Hughes Medical Institute, NIH/National Institutes of Health, Welch Foundation, Boehringer Ingelheim Fonds.
Combining condensin exhaustion with a treatment that increases the levels of histone acetylation triggered massive chromatin decompaction in dividing cells, and perforation of chromosomes by microtubules.
They then established an assay to probe the solubility of chromatin by fragmenting mitotic chromosomes into small pieces. The fragments of mitotic chromosomes formed beads of liquid chromatin, but when the acetylation level was increased, the chromatin pieces liquified in the cytoplasm.
Chromatin compaction controlled by histone acetylation will avoid the perforation of the chromosomes by microtubules. “Amidst this complex system, the distinct physical homes are given to the chromosomes by changing the levels of histone acetylation, a chemical adjustment within the chromatin fiber,” states IMBA Group Leader Daniel Gerlich.
