How cells correctly choose active genes
Formation of transcription factories resembles condensation of liquids


Date:
November 5, 2021
Source:
Karlsruhe Institute of Technology
Summary:
It is essential for cells to control precisely which of the
many genes of their genetic material they use. This is done
in so-called transcription factories, molecular clusters in
the nucleus. Researchers have now found that the formation of
transcription factories resembles the condensation of liquids. Their
findings will improve the understanding of causes of diseases and
advance the development of DNA-based data storage systems.



FULL STORY ==========================================================================
It is essential for cells to control precisely which of the many
genes of their genetic material they use. This is done in so-called transcription factories, molecular clusters in the nucleus. Researchers of Karlsruhe Institute of Technology (KIT), Friedrich-Alexander-Universita"t Erlangen-Nuremberg (FAU), and Max Planck Center for Physics and Medicine (MPZPM) have now found that the formation of transcription factories
resembles the condensation of liquids.

Their findings will improve the understanding of causes of diseases and
advance the development of DNA-based data storage systems. The scientists report in Molecular Systems Biology.


========================================================================== Human genetic material contains more than 20,000 different genes. But each
cell only uses a fraction of the information stored in this genome. Hence, cells have to control precisely which genes they use. If not, cancer
or embryonal growth disorder may develop. So-called transcription
factories play a central role in the selection of active genes. "These factories are molecular clusters in the nucleus that combine the
correct selection of active genes and the read- out of their sequence
at a central location," Lennart Hilbert explains. The Junior Professor
for Systems Biology/Bioinformatics at the Zoological Institute (ZOO)
of KIT also heads a working group at KIT's Institute of Biological and
Chemical Systems -- Biological Information Processing (IBCS-BIP).

Setup and Start within a Few Seconds For decades, cellular and molecular biologists have studied how transcription factories are set up and taken
into operation within a few seconds. Results obtained so far suggest
relevance of processes known from industrial and technical polymer and
liquid materials only. Current research focuses on phase separation as
a central mechanism. In everyday life, phase separation can be observed
when separating oil from water. It has not yet been clear, however,
how exactly phase separation contributes to the setup of transcription factories in living cells.

Researchers from KIT's Institute of Biological and Chemical Systems
(IBCS), Zoological Institute (ZOO), Institute of Applied Physics (APH),
and Institute of Nanotechnology (INT), in cooperation with scientists
from FAU and MPZPM in Erlangen and the University of Illinois at Urbana-Champaign/USA, have now gained new findings on the formation
of transcription factories: It is similar to the condensation of
liquids. This is reported in Molecular Systems Biology.

The first co-authors are Agnieszka Pancholi of IBCS-BIP and ZOO and Tim Klingberg of FAU and MPZPM.

Latest Light Microscopy Combined with Computer Simulations In their publication, the researchers point out that condensation to form
transcription factories resembles steamy glasses or windows. Liquid
condenses in the presence of a receptive surface only, but then very
quickly. In the living cell, specially marked areas of the genome
are used as condensation surfaces. The liquid-coated areas allow for
the adhesion of relevant gene sequences and additional molecules that eventually activate the adhering genes.

These findings were obtained by interdisciplinary cooperation. Zebrafish embryos were studied with latest light microscopes developed by Professor
Gerd Ulrich Nienhaus's Chair at APH. These observations were then linked
to computer simulations at the FAU Chair for Mathematics headed by
Professor Vasily Zaburdaev. Combination of observations and simulations
makes the condensation process reproducible and explains how living
cells can set up transcription factories rapidly and reliably.

New understanding of condensed liquids in living cells recently resulted
in entirely new approaches to treating cancer and diseases of the
nervous system.

These approaches are now being pursued by startups developing new
drugs. Other research activities focus on the use of DNA sequences
as digital data storage systems. Meanwhile, principle feasibility of
DNA-based data storage systems has been demonstrated by several working
groups. Reliable storage and read-out of information in such DNA storage
media still represent big challenges. "Our work shows how the biological
cell organizes such processes rapidly and reliably.

The computer simulations and functional concepts developed by us can
be transferred directly to artificial DNA systems and can support their design," Lennart Hilbert says.

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


========================================================================== Journal Reference:
1. Agnieszka Pancholi, Tim Klingberg, Weichun Zhang, Roshan Prizak,
Irina
Mamontova, Amra Noa, Marcel Sobucki, Andrei Yu Kobitski,
Gerd Ulrich Nienhaus, Vasily Zaburdaev, Lennart Hilbert. RNA
polymerase II clusters form in line with surface condensation
on regulatory chromatin. Molecular Systems Biology, 2021; 17 (9)
DOI: 10.15252/msb.202110272 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211105134631.htm

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