Nav: Home

DNA structure influences the function of transcription factors

September 02, 2016

Substances known as transcription factors often determine how a cell develops as well as which proteins it produces and in what quantities. Transcription factors bind to a section of DNA and control how strongly a gene in that section is activated. Scientists had previously assumed that gene activity is controlled by the binding strength and the proximity of the binding site to the gene. Researchers at the Max Planck Institute for Molecular Genetics in Berlin have now discovered that the DNA segment to which a transcription factor binds can assume various spatial arrangements. As a result, it alters the structure of the transcription factor itself and controls its activity. Neighbouring DNA segments have a significant impact on transcription factor shape, thus modulating the activity of the gene.

For a car to move, it is not enough for a person to sit in the driver's seat: the driver has to start the engine, press on the accelerator and engage the transmission. Things work similarly in the cells of our body. Until recently, scientists had suspected that certain proteins only bind to specific sites on the DNA strand, directing the cell's fate in the process. The closer and more tightly they bind to a gene on the DNA, the more active the gene was thought to be. These proteins, known as transcription factors, control the activity of genes.

A team of scientists headed by Sebastiaan Meijsing at the Max Planck Institute for Molecular Genetics have now come to a different conclusion: The researchers discovered that transcription factors can assume various shapes depending on which DNA segment they bind to. "The shape of the bond, in turn, influences whether and how strongly a gene is activated," Meijsing explains.

Consequently, transcription factors can bind to DNA segments without affecting a nearby gene. As in our car analogy, the mere presence of a "driver" is evidently not sufficient to set the mechanism in train. Other factors must also be involved in determining how strongly a transcription factor activates a gene.

Glucocorticoid receptor is also a transcription factor

One example is glucose production in the liver. If the blood contains too little glucose, the adrenal glands release glucocorticoids, which act as chemical messengers. These hormones circulate through the body and bind to glucocorticoid receptors on liver cells. The receptors simultaneously act as transcription factors and regulate gene activity in the cells. In this way, the liver is able to produce more glucose, and the blood sugar level rises again.

"Sometimes glucocorticoid receptor binding results in strong activation of neighbouring genes, whereas at other times little if anything changes," Meijsing reports. The scientists found that the composition of DNA segments to which the receptors bind help determine how strongly a gene is activated. However, these segments are not in direct contact with the receptors acting as transcription factors; they only flank the binding sites. Yet, that is evidently enough to have a significant influence on the interaction.

"The structure of the interface between the transcription factor and genome segments must therefore play a key role in determining gene activity. In addition, adjacent DNA segments influence the activity of the bound transcription factors. These mechanisms ultimately ensure that liver cells produce the right substances in the right amounts," Meijsing says.

Medical applications

The findings could also have medical applications. Many DNA variants associated with diseases belong to sequences that evidently control the activity of transcription factors. "Scientists had previously assumed that these segments exert an effect by inhibiting the binding of transcription factors, thus impeding the activity of neighbouring genes," Meijsing says. "Our findings have now shown that some of these segments may not influence the contact directly but nevertheless reduce the activation state of the associated transcription factor."
Original publication: Stefanie Schöne, Marcel Jurk, Mahdi Bagherpoor Helabad, Iris Dror, Isabelle Lebars, Bruno Kieffer, Petra Imhof, Remo Rohs, Martin Vingron, Morgane Thomas-Chollier, Sebastiaan H. Meijsing
Sequences flanking the core binding site modulate glucocorticoid receptor structure and activity
Nature Communications; 1 September, 2016


Related Dna Articles:

A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
Switching DNA and RNA on and off
DNA and RNA are naturally polarised molecules. Scientists believe that these molecules have an in-built polarity that can be reoriented or reversed fully or in part under an electric field.
New DNA synthesis technique promises rapid, high-fidelity DNA printing
Today, DNA is synthesized as an organic chemist would, using toxic chemicals and error-prone steps that limit accuracy and thus length to about 200 base pairs.
The changing shape of DNA
The shape of DNA can be changed with a range of triggers including copper and oxygen - according to new research from the University of East Anglia.
More Dna News and Dna Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.