Untwisting DNA reveals new force that shapes genomes
Transcription generates a force that moves across DNA strands like
ripples through water

Date:
July 22, 2021
Source:
Center for Genomic Regulation
Summary:
Advances in microscopy reveal how the human genome organises itself
in three-dimensional space at much higher resolution than previously
possible. A new study finds that transcription generates a force
that moves across DNA strands like ripples through water. The
discovery may have future implications for the understanding of
genetic diseases such as Cornelia de Lange syndrome, developmental
disorders linked to chromatin folding, and open new avenues of
research in genome fragility and cancer development.



FULL STORY ========================================================================== Advances in microscopy have enabled researchers to picture loops of
DNA strands for the first time. The images reveal how the human genome organises itself in three-dimensional space at much higher resolution
than previously possible.


==========================================================================
The findings, published in a new study in the journal Molecular Cell, also reveal that the process of DNA being copied into RNA -- transcription -
- indirectly shapes the architecture of the genome. An international
team led by Pia Cosma at the Centre for Genomic Regulation (CRG) in
Barcelona and Melike Lakadamyali at the Perelman School of Medicine
at the University of Pennsylvania in the United States found that
transcription generates a force that moves across DNA strands like
ripples through water.

Known as supercoiling, the force causes structural proteins known
as cohesins to 'surf' across DNA strands, changing the scaffold's
architecture and morphing the overall shape of the genome. While it
is known that genome organization regulates gene transcription, it is
the first-time researchers have found transcription to impact genome organization the other way round through supercoiling.

According to the researchers, the discovery of this new force may have
future implications for the understanding of genetic diseases such as
Cornelia de Lange syndrome, which is caused by mutations in genes encoding
for cohesin or cohesin regulators. The findings may also be relevant for developmental disorders linked to how chromatin folds, as well as opening
new avenues of research in genome fragility and cancer development.

The researchers studied the biological mechanisms that enable two
metres of DNA to be squeezed into a tight space in each human cell. In
this condensed state, the DNA, also known as chromatin, contains many
loops that bring together different regions of the genome that would
normally be far apart. The resulting physical proximity is important for transcribing DNA into RNA which then makes proteins, making chromatin
looping a fundamental biological mechanism for human health and disease.

According to Vicky Neguembor, Staff Scientist at the CRG and first
author of the paper, "Chromatin looping is what allows individual cells
to switch different information on and off, which is why for example a
neuron or a muscle cell with the same genomic information can still behave
so differently. Loops are also one of the ways the genome gets compacted
to fit into the nucleus." "What we have found is important because it
shows the biological process of transcription plays an additional role
beyond its fundamental task of creating RNA that eventually turn into
proteins. Transcription indirectly compacts the genome in an efficient
manner and helps different regions of the genome talk to each other."
Previous techniques used to study this process could predict where loops
were located but not their actual shape or how they look like within
the cells. To improve image resolution, the researchers used a special
type of microscopy that use high-power lasers under specific chemical conditions to track the blinking of fluorescent molecules. The technique provides ten times higher resolution than conventional microscopy,
and combined with advanced imaging analysis techniques the researchers
were able to identify chromatin loops, and the cohesins that hold the
structure together like paper clips, within intact cells.

========================================================================== Story Source: Materials provided by Center_for_Genomic_Regulation. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Maria Victoria Neguembor, Laura Martin, A'lvaro Castells-Garci'a,
Pablo
Aurelio Go'mez-Garci'a, Chiara Vicario, Davide Carnevali, Jumana
AlHaj Abed, Alba Granados, Ruben Sebastian-Perez, Francesco
Sottile, Je'ro^me Solon, Chao-ting Wu, Melike Lakadamyali, Maria
Pia Cosma. Transcription- mediated supercoiling regulates genome
folding and loop formation.

Molecular Cell, 2021; DOI: 10.1016/j.molcel.2021.06.009 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210722113007.htm

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