Drosophila
Condensin II subunit Chromosome - associated protein D3 regulates cell fate determination through non-cell-autonomous signaling.
Large amounts
of condensin also accumulate at areas where RNA is created.
This type of yeast shares many important genes with us and also has one of the two known
condensin complexes in humans.
Therefore, physical force at the kinetochore is diffused and inefficiently transmitted to chromosomal arm regions, resulting in chromosomal segregation defects
in condensin mutant.
By combining the fission yeast, mouse, and human systems with the latest genomic, genetic, cell biological, and biochemical approaches, we seek to determine
how condensin and cohesin organize the functional 3D genome structures and participate in various biological processes, including transcriptional regulation and chromosomal dynamics, and how they contribute to oncogenic processes.
Figure 2:
Condensin subunit SMC4 tagged with mEGFP and nanobody - stained in a prometaphase HeLa cell visualised by an astigmatic 3D STORM microscope.
It turns out cells use two different ring - shaped proteins
called condensins to do...
The cells on the right produced
mutant condensin and their chromosomes were unable to segregate properly.
The looping speed was found to be remarkably high: up to 1500 base pairs of DNA can be reeled in
by condensin per second.
At this point, the relevant biochemical processes by
which condensin works remain to be apprehended.
One theory stated that
condensin works like a hook that can grasp and connect DNA within the jumble of DNA, thus tying it together.
These data provide compelling evidence that
condensin indeed reels in DNA to form loops.
OIST researchers bumped up the heat from 20 degrees to 36 degrees centigrade over 9 minutes, and found that
condensin accumulated around heat - shock protein (Hsp) genes after replication.
Another theory suggested that the ring -
shaped condensin pulls the DNA inwards to create a loop.
Researchers from the Kavli Institute of Nanoscience at Delft University and EMBL Heidelberg now managed for the first time to isolate and film the process, and witnessed — in real time — how a single protein complex called
condensin reels in DNA to extrude a loop.
The OIST researchers found that the largest amount of
condensin aggregates at the centromere, the central knot tying together the two replicated chromosomes.
Amazingly, we could then see a
single condensin bind and start extruding a loop.»
Apparently, with tension,
condensin seems to struggle more to create a loop.
Unexpectedly, the loop extrusion is asymmetric: «We saw that
condensin docks onto DNA and anchors itself there, and then starts reeling in DNA from one side only.»
Problems with the protein family to which
condensin belongs — the SMC proteins — are related to hereditary conditions such as Cornelia de Lange Syndrome.
Using an important genomic methodology, referred to as ChIA - PET (Chromatin Interaction Analysis by Paired - End Tag sequencing), we have been able to
capture condensin - and cohesin - mediated gene contacts throughout the fission yeast genome.
Our results have revealed that
although condensin and cohesin bind to the same gene loci, they direct different association networks (Figure).
Cohesin mediates local contacts, i.e. between loci positioned within 100 kb (red),
whereas condensin drives longer - range contacts (blue).
Excitingly, our study points out that
condensin plays an important role in cellular senescence, a major tumor suppression mechanism.
Cohesin forms small topological chromatin domains of approximately 100 kb,
while condensin organizes 300 kb — 1 Mb domains.
In the figure:
Condensin triggers cellular senescence and its associated genome organization.
We have shown that the
human condensin complex functions in global 3D genome reorganization during the important process of cellular senescence (Yokoyama et al..
Condensin expression in non-senescent human cell (left) induces senescence and completely transforms global genome architecture (right), which is referred to as Senescence - Associated Heterochromatic Foci (SAHF).
In the figure: ChIA - PET genomic analyses successfully
mapped condensin (left) and cohesin (right)- mediated gene contacts throughout the fission yeast genome.
Condensin II subunit dCAP - D3 restricts retrotransposon mobilization in Drosophila somatic cells.
How condensin and cohesin govern the 3D structure of the eukaryotic genome is an exciting research area.
It turns out cells use two different ring - shaped proteins
called condensins to do both actions, imaging and computer simulations reveal.
The researchers also engineered a yeast strain where a
mutant condensin was produced by the cell when it went into figurative labor.
In a cover article in Science last November, scientists from Delft and collaborating labs showed that
condensin indeed has the motor function needed for such loop extrusion.
Centromeres associate with dispersed gene loci, and these gene contacts are mediated
by condensin.
(C)
In condensin mutant, highly active genes do not associate with centromeres.
The protein complex, called
condensin, is one of many that become active when cells replicate.
Larger cells need more energy to survive and
condensin could be crucial to maintaining appropriate DNA content and cell sizes across cellular generations.
The OIST researchers speculate that
condensin is trimming the hedgerow of the genome during the replication and dividing phase.
Thus,
condensin is crucial to passing on genes correctly.
Where the second type of
condensin, which is present in humans and other multicellular organisms, binds during cell division is another future line of inquiry.
Condensin I subdivides large loops into smaller nested loops that allow for more space - efficient packing.
Condensin II shapes a chromosome into large loops and then forms a helical scaffold for the loops to wind around.
Condensin is also crucial in the organisation of the chromosomes during cell division, and errors in the process can result in cancer.
This video shows how
a condensin protein gradually causes DNA to extrude a DNA loop over time.
This added an important new piece to the puzzle, but as Kim Nasmyth from Oxford University — one of the leading scientists in the field of DNA organisation — noted in the accompanying perspective in Science, «the discovery that
condensin is a DNA translocase is certainly consistent with the idea that it functions as a loop extruder, but by no means proves it.
Artist's impression of how
a condensin protein complex extrudes a loop of DNA for the spatial organization of chromosomes.