Take my hand and ride with me -- Over the genome

October 02, 2018

The development of an adult organism starts with a fertilized egg that differentiates into hundreds of specialized cell types contained in tissues and organs. How these cell fate changes happen is intensely investigated all over the world. What we know is that all our cells contain the same genetic information, therefore development involves the selective regulation of genes contained in the DNA. The proteins that turn on or off these genes are called transcription factors. Similar mechanisms operate when a stem cell in the adult body, such as the blood stem cell, specializes into cell types needed for different functions. To ensure correct gene regulation additional kinds of proteins are required, such as enzymes that modify proteins that wrap around the DNA or even the DNA itself, thus fine tuning this complex process. Interestingly, alterations of these proteins due to mutations leads to aberrant gene regulation and often results in the formation of cancer.

In a paper published in Cell Stem Cell, researchers at the Centre for Genomic Regulation (CRG) led by Thomas Graf in collaboration with scientists from the Institut de Biologie de l'Ecole Normale Supérieure in Paris and from CNAG-CRG and Harvard Medical School, studied this complex process. They focused their attention on an enzyme named Tet2, which plays a crucial role in the formation of pluripotent stem cells and in blood cell differentiation.

Tet2 is a driving force of cell fate decisions that promotes gene expression by chemically modifying the DNA. To do so, it needs to bind DNA but, surprisingly, cannot do it by itself. So, the question arises as to what brings the Tet2 enzyme to regions in the DNA where it does its job?

Now, Graf and colleagues have described that Tet2 is brought to the DNA by specific proteins with which it can interact. They identified three different transcription factors, each of which can ´take the enzyme by the hand´ and guide it to different sets of target genes needed for cell fate specification. Unexpectedly, therefore a number of different proteins can bring Tet2 to regions of the DNA where and when it is needed.

"We have studied the mechanism by Tet2 acts by monitoring the dynamics of DNA modifications during induced pluripotent stem cell reprogramming. Our data have helped to answer an open question in the field, relevant not only for embryo development and differentiation but also for cell reprogramming and cancer," explains Thomas Graf, principal investigator of the study and CRG group leader.

"Our results will be helpful for other researchers working in leukemia and other types of cancer, in which Tet2 is involved," says José Luis Sardina, first and co-corresponding author of the paper. "Our new data will be available for the clinical research community. This is another example of how fundamental research uncovering basic mechanisms of gene regulation might also have medical applications, in this case, in cancer and cell regeneration," he concludes.

The study also reported another unexpected finding, namely that transcription factors can recruit Tet2 to specific DNA regions without the displacement of proteins that wrap around the DNA, contained in so called ´nucleosomes´. This represents a novel way in which transcription factors interact with the genome, acting as 'pioneers' for the positioning of Tet2. Says Graf, "It will now be fascinating to find out the role for cell fate decisions of the regions in the genome that are bound by these pioneer factors".
-end-


Center for Genomic Regulation

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.