Nav: Home

Unlocking the genome

June 04, 2018

A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells. These findings shed new light on the biological mechanisms of gene regulation and open up potential new avenues for cellular reprogramming.

The human body consists of trillions of cells and each of them contains all of the DNA that makes us unique as human beings. At any given time, the majority of our DNA is wrapped around histone proteins and stacked into chromatin. Not only to conserve space, but also to allow for the dynamic regulation of gene expression. So-called pioneer factors can directly bind condensed chromatin, making specific regions of the DNA accessible and enabling the regulation of nearby genes.

Stein Aerts, professor at VIB-KU Leuven, is interested in understanding the fine-tuned processes that govern this regulation: "Over the last decade, we have seen a shift from studying genes to studying gene regulation. Now that we can systematically profile genomes, epigenomes and transcriptomes, the challenge is to discover the rules that link DNA sequence with chromatin state and gene expression. In ot¬her words, we try to disentangle the regulatory code of our genome."

Grainyhead, a pioneer factor for epithelial genes

Aerts and his team set out to study how DNA sequence information, chromatin accessibility and gene expression are linked in epithelial cells. These cells line the outer surfaces of organs and form the outer layer of the skin.

Jelle Jacobs, doctoral student in the Aerts lab, explains: "Using a combination of computational biology and in vivo experiments, we found that access to the DNA regions that are relevant for epithelial cells is governed by a protein called Grainyhead. Grainyhead is necessary to 'unlock' these specific DNA regions, which in turn allows other players to move in and turn genes on or off."

The scientists started their research in fruit flies, but could confirm that a similar mechanism is at play in humans. Jacobs: "Our results provide strong evidence for a hierarchical model of gene control--with Grainyhead at the top--that is conserved across all animals."

A key to unlock DNA

Previous research has shown that in the absence of Grainyhead, developmental problems arise and wound healing is disturbed. Loss of Grainyhead has also been linked to increased cancer metastasis. Explaining these observations had been tricky, as relevant genes were found to be upregulated in one instance, but downregulated in another.

These earlier findings make more sense now that Grainyhead is uncovered to sit at the very top of the regulatory hierarchy in epithelial cells. It essentially acts as a key that can be used to access the relevant DNA regions.

According to Aerts, such knowledge could be extremely useful: "We can now explore if we can use this lock-and-key system to open up or close off other parts of the genome in a controlled way as well. This could be helpful for example in regenerative medicine, to direct cells to turn on specific genetic programs for skin cells or any other type of cells."-

What's in a name?

Genes identified in fruit flies are often named after the characteristics of the mutant fly. When the grainyhead gene is absent, fly embryos are not viable, but mutations lead to embryos with "grainy" and discontinuous head skeletons.
-end-
Publication

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes, Jacobs et al. 2018 in Nature Genetics

Questions from patients

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

VIB (the Flanders Institute for Biotechnology)

Related Dna Articles:

In one direction or the other: That is how DNA is unwound
DNA is like a book, it needs to be opened to be read.
DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.
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.
More Dna News and Dna Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.