Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene regulation - it's all in the DNA

22.10.2008
GPEARI / MCTES - Gabinete de Planeamento, Estratégia, Avaliação e Relações Internacionais / Ministério da Ciência, Tecnologia e Ensino Superior

Scientists in Cambridge, UK, using a mouse with a human chromosome in its cells, discovered that gene expression, contrary to what was previously thought, is mostly controlled by regulatory DNA sequences.

Mice and humans (and most vertebrates) share the majority of their genes but a distinct gene regulation – so, when and where these shared genes become activated – assures their many individual characteristics, and knowledge of this regulation is crucial if we want one day to be able to control gene expression.

These new results - just published on the journal Science – challenge current belief that gene regulation is mediated by a combination of many factors, implying that, to be able to understand the mechanisms behind different specialised cells, scientists will have to track species-specific regulatory pieces of DNA, what will be no easy task. The research has implications in the study of phenomena as diverse as genetic diseases, tissue and organ growth and even cloning.

In the last two decades new techniques to study the genome have revealed how genetically similar we are to other vertebrates with humans having more than 99% of gene homology (similarity) with chimps or, even more surprisingly, as much as 85% with mice. Still, we are undoubtedly very different and the explanation relies on different patterns of gene regulation throughout the body, which need to be understood if we want to comprehend (and one day control) how different cells, tissues and organs originate.

In order to investigate how gene regulation is mediated Michael D. Wilson, Nuno L. Barbosa-Morais, Duncan T. Odom (Cancer Research UK and University of Cambridge) and colleagues (London and Minnesota took advantage of an unique mouse called Tc1, which was developed to study Down syndrome (a disease where patients have an extra chromosome 21) and has an extra (human) chromosome 21 in addition to its normal mouse genome.

“What makes this model so extraordinary is that we have an entire chromosome of a species inside the cellular environment of another species, allowing us to find if gene expression is determined by the (human) DNA sequence or by the (mouse) environment” highlights Nuno Barbosa-Morais, a Portuguese researcher and one of the study’s first authors.

To compare gene expression patterns in the human and mouse chromosomes the researchers analysed the behaviour of set of proteins called transcription factors. When a gene is expressed, the first step - called transcription - consists in passing the information on the DNA to a molecule of RNA. Transcription factors - by binding to specific (activator or repressor) sequences of DNA adjacent to the genes they regulate – control which genetic information is transferred to the RNA during transcription, and consequently which genes are expressed. In fact, genes are often surrounded by several binding sites and depending on the combinations of transcription factors binding where, the genes are activated or repressed.

For the experiments in this article Wilson, Barbosa-Morais and colleagues compared binding patterns in the human chromosome and its mouse equivalent (equivalent means with a common ancestor and containing genes with similar functions) in Tc1 mouse liver cells, and again in both these chromosomes but in human and mouse normal liver cells respectively.

To their surprise, the behaviour of the transcription factors in the human chromosome 21– so their binding patterns to the different activator/suppressor zones in the DNA – was the same, whether this chromosome was in Tc1 or human hepatic cells, while very different from the patterns seen on its equivalent mouse chromosome. Furthermore, other markers of gene expression, as well as the RNA produced, were also very similar whether chromosome 21 was in human or Tc1 hepatic cells.

In conclusion, Wilson, Barbosa-Morais, Odom and colleagues’ results showed that the human chromosome, despite being in a full mouse environment, still behaved in “a human form”, showing that gene regulation is mostly the result of DNA regulatory sequences, at least in liver cells. Factors like cellular environment, DNA packing, outside cues or even the nature of transcription factors – as we see here, mouse transcription factors have no problems working in human DNA – all previously believed to affect regulation, are shown to have little effect on gene expression.

If this result is proved to be a generalised characteristic of cells, it is a finding that will question a series of widespread believes and strategies of biology. For example, one way scientists search for new active (or functional) genes is by looking for similar sequences in corresponding chromosomes of different species. What Wilson, Barbosa-Morais, Odom and colleagues’ results reveal that it is that those sequences that are not shared between species that ultimately determine if a gene is functional or not , implying that a much more detailed analysis of the DNA needs to be done to effectively understand our genetic blueprint.

Tissue and organ growing, and even cloning, are just some of the fields that can be potentially affected by these results. For example, it has been seen that if we collect all the transcription factors in a kidney cell and transfer them to a brain cell (where we inactivate all its brain-specific transcription factors) we could turn the brain cell into a kidney one. Or that if we put a “pro-cell” in a specific cellular environment it could develop into the cell and tissue corresponding to that environment. The new data by Wilson and colleagues - indicating that DNA regulatory sequences are the major force behind gene regulation - bring a new player into tissue and organ development, and although apparently making things more complicated, it will, no doubt, contribute to a better comprehension of the mechanisms behind cell specialisation.

Finally, these results can be important to understand better the mechanism behind disorders with a genetic origin whatever neurodegenerative and development diseases or even cancer. Like Barbosa-Morais says: “in diseases like cancer our work alerts for the crucial need to focus on risk factors in the DNA sequence and not just on examining developmental changes in the cell”.

When the genome started to be sequenced in the 1990s scientists knew that we were still very far from fully identifying our genes, and even further from understanding their function, but only in the last 10 years we have come to realise the real complexity behind gene expression. In fact, while less than 3% of the human DNA seems to be genes, more and more DNA (and RNA) that are not expressed into proteins - so not “real” genes –are discovered to affect gene expression. Transcription factors, on the hand, are now believed to be around 10% of all genes suggesting that the number of binding combinations switching genes on or off is also very large and will need a lot of work to be fully understood. Although we are still a long way to fully understand the intricacies of gene expression, Wilson, Barbosa-Morais, Odom and colleagues’ research is no doubt an important step in the right direction

Piece by Catarina Amorim (catarina.amorim at linacre.ox.ac.uk)

Contacts for the authors of the original paper
Duncan T. Odom - duncan.odom@cancer.org.uk
Nuno Barbosa-Morais - Nuno.Barbosa-Morais@cancer.org.uk

Catarina Amorim | alfa
Further information:
http://www.sciencemag.org/cgi/content/abstract/1160930

More articles from Life Sciences:

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

nachricht Wintering ducks connect isolated wetlands by dispersing plant seeds
22.02.2017 | Utrecht University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Positrons as a new tool for lithium ion battery research: Holes in the electrode

22.02.2017 | Power and Electrical Engineering

New insights into the information processing of motor neurons

22.02.2017 | Life Sciences

Healthy Hiking in Smart Socks

22.02.2017 | Innovative Products

VideoLinks
B2B-VideoLinks
More VideoLinks >>>