How liquid-like protein droplets collectively read DNA regions to switch
on genes

Date:
February 3, 2022
Source:
Max Planck Institute of Molecular Cell Biology and Genetics
(MPI-CBG)
Summary:
When an organism develops, dividing cells specialize to form the
variety of tissues and organs that build up the adult body, while
keeping the same genetic material -- contained in our DNA. In a
process known as transcription, parts of the DNA -- the genes --
are copied into a messenger molecule -the ribonucleic acid (RNA)
-- that carries the information needed to produce proteins, the
building blocks of life.



FULL STORY ==========================================================================
Life starts with one cell. When an organism develops, dividing cells
specialize to form the variety of tissues and organs that build up the
adult body, while keeping the same genetic material -- contained in our
DNA. In a process known as transcription, parts of the DNA -- the genes
-- are copied into a messenger molecule -the ribonucleic acid (RNA) --
that carries the information needed to produce proteins, the building
blocks of life. The parts of our DNA that are read and transcribed
determine the fate of our cells. The readers of the DNA are proteins
called transcription factors: they bind to specific sites on the DNA and activate the transcription process. How they recognize which location on
the DNA they need to bind to and how these are distinguished from other
random binding sites in the genome remains an open question. Scientists at
the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)
and the Max Planck Institute for the Physics of Complex Systems (MPI-PKS),
both located in Dresden, show that thousands of individual transcription factors team up and interact with each other. They collectively wet the
DNA surface by forming liquid droplets that can identify clusters of
binding sites on the DNA surface.


========================================================================== Transcription, one of the most fundamental cellular processes, is the
action by which the information contained in the DNA is transcribed
into the messenger molecule RNA. This "message" is later translated into proteins. Deciding which parts of the DNA are transcribed at any given
moment is crucial for proper development to maintain the health of an
organism, because many diseases are likely to occur when the genetic
programs are not executed correctly. The decision as to which genes are transcribed is made by a complex network of regulatory proteins called transcription factors. While these factors bind to short DNA sequences,
the recognition of clusters of many such sequences is required to switch
on nearby genes.

The research groups of Stephan Grill and Anthony Hyman, both directors at
the MPI-CBG, and the group of Frank Ju"licher, director at the MPI-PKS investigated in their recent study in the journal Nature Physics how transcription factors find and recognize clusters of many specific
DNA sequences where they can bind and lead to gene activation. To
find this out, the researchers followed an interdisciplinary approach, combining expertise in experimental and theoretical biophysics with cell biology. Jose A. Morin, one of the first authors of the study, explains:
"We employed optical tweezers -- a technology that uses lasers to isolate
and manipulate very small objects such as single DNA molecules - -
combined with confocal microscopy to look at them individually. With
optical tweezers it is possible to capture a single DNA molecule and
with confocal microscopy we can observe transcription factors binding
and forming protein condensates at their preferred DNA sequences. The
fact that we can study this process one molecule at the time allowed
us to detect interactions otherwise blurred by the complexity of the
living cell." Sina Wittmann, another first author, adds: "With the help
of the physicists, we were able to understand how transcription factors communicate with each other and assemble through team work. They undergo
what is called a prewetting transition to form liquid-like droplets,
which are similar to the drops on a mirror in your bathroom after a
shower. These condensates are filled with thousands of transcription
factors.

Assembled in this way, the transcription factors can now identify
the correct DNA region by reading out DNA sequence." Stephan Grill
summarizes: "We now have a possible mechanistic explanation for
the localisation of transcription factors along the genome. This is
essential to understand how gene expression is regulated. Since we know
that this regulation breaks down in developmental diseases and cancer,
these new results give us a clearer picture of how these diseases
occur. This knowledge is important to think about new therapeutic
options that take the team work of transcription factors into account." ========================================================================== Story Source: Materials provided by Max_Planck_Institute_of_Molecular_Cell_Biology_and
Genetics_(MPI-CBG). Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jose A. Morin, Sina Wittmann, Sandeep Choubey, Adam Klosin, Stefan
Golfier, Anthony A. Hyman, Frank Ju"licher, Stephan
W. Grill. Sequence- dependent surface condensation of a pioneer
transcription factor on DNA.

Nature Physics, 2022; DOI: 10.1038/s41567-021-01462-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220203122912.htm

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