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ADVANCE IN CHEMICAL EPIGENETICS

Re­searchers Write and Erase DNA Methylation with Light

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A man on the left and a woman and man on the right in the lab wearing white coats. © TU Dort­mund
Prof. Daniel Summerer, Dr. Shubhendu Palei and Jan Wolffgramm (from left) has achieved an im­por­tant advance in chemical epigenetics.

Scientists at TU Dort­mund Uni­ver­sity have achieved an im­por­tant advance in the field of chemical epigenetics: In two studies, they describe for the first time how light can be used to directly switch the writing and erasure of DNA methylation. A central process in human biology, DNA methylation regulates, for example, the development of embryos and the onset of cancer. The re­search results have been published in two re­nowned scientific journals.

To understand what the researchers have achieved, one must first recall the basic biological principles: DNA methylation is a chemical modification of the basic building blocks of DNA – the hereditary substance of a cell. Through this modification, a cell can flexibly switch its genes on or off. It has long been known that abnormal or missing methylations of DNA building blocks can disturb cell growth and transform a healthy cell into a proliferating cancer cell. For this reason, sci­en­tists would like to find out exactly how this process takes place in the cell.

Methylation is “written” on DNA, or “erased” from it, by specific enzymes. Previously, however, it has not been possible to precisely switch the responsible enzymes directly in cells to investigate the subsequent processes in detail. Prof. Daniel Summerer’s re­search group in the Chem­is­try and Chemical Biology Department at TU Dort­mund Uni­ver­sity has now been able to do this for the first time – with the help of light. This work could provide a foundation for new insights, never before possible, into the sequence and speed of the processes responsible for the changes cells undergo during embryonic development and the onset of cancer.

How light can be used in DNA methylation

Chemical biologists Dr. Shubhendu Palei and Jan Wolffgramm from the re­search group use light as a stimulus because it offers very high spatial and temporal resolution and, in addition, is non-invasive – a perfect fit for in­ves­ti­gat­ing local and rapid processes in intact cells and whole organisms. First they had to place particular artificial amino acids that can be cleaved by light at key sites on the enzyme. At specific points in time, they then were able to activate the enzymes with brief irradiation in the cells and observe what happens next. In this way, the team investigated the effect of various cancer-relevant mutations on the enzymes’ activity and obtained the first insights into which genes this activity switches on or off, in what sequence, and how strongly. In addition the team managed to develop programmable “writer enzymes” that can selectively methylate specific sequences in the genome, thus enabling the strength of this methylation to be precisely con­trolled through the duration of the light irradiation.

These studies, published in the Journal of the American Chemical Society and An­ge­wand­te Chemie, were conducted within the frame­work of the proj­ect EPICODE. For this proj­ect, starting in 2017, the European Research Council awarded Prof. Daniel Summerer an ERC Consolidator Grant of nearly two million euros. Other collaborators on these studies were Prof. Michal Schweiger’s epigenetics and tumor biology re­search group at the Uni­ver­sity of Cologne and Dr. Petra Janning of the Max Planck In­sti­tute for Molecular Physiology in Dort­mund.

Links to the original publications:

Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization

Light‐Activation of DNA‐Methyltransferases

 

Contact for further in­for­mation:

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The campus of TU Dort­mund Uni­ver­sity is located close to interstate junction Dort­mund West, where the Sauerlandlinie A 45 (Frankfurt-Dort­mund) crosses the Ruhrschnellweg B 1 / A 40. The best interstate exit to take from A 45 is “Dort­mund-Eichlinghofen” (closer to South Cam­pus), and from B 1 / A 40 “Dort­mund-Dorstfeld” (closer to North Cam­pus). Signs for the uni­ver­si­ty are located at both exits. Also, there is a new exit before you pass over the B 1-bridge leading into Dort­mund.

To get from North Cam­pus to South Cam­pus by car, there is the connection via Vo­gel­pothsweg/Baroper Straße. We recommend you leave your car on one of the parking lots at North Cam­pus and use the H-Bahn (suspended monorail system), which conveniently connects the two campuses.

TU Dort­mund Uni­ver­sity has its own train station (“Dort­mund Uni­ver­si­tät”). From there, suburban trains (S-Bahn) leave for Dort­mund main station (“Dort­mund Hauptbahnhof”) and Düsseldorf main station via the “Düsseldorf Airport Train Station” (take S-Bahn number 1, which leaves every 20 or 30 minutes). The uni­ver­si­ty is easily reached from Bochum, Essen, Mülheim an der Ruhr and Duisburg.

You can also take the bus or subway train from Dort­mund city to the uni­ver­si­ty: From Dort­mund main station, you can take any train bound for the Station “Stadtgarten”, usually lines U41, U45, U 47 and U49. At “Stadtgarten” you switch trains and get on line U42 towards “Hombruch”. Look out for the Station “An der Palmweide”. From the bus stop just across the road, busses bound for TU Dort­mund Uni­ver­sity leave every ten minutes (445, 447 and 462). Another option is to take the subway routes U41, U45, U47 and U49 from Dort­mund main station to the stop “Dort­mund Kampstraße”. From there, take U43 or U44 to the stop “Dort­mund Wittener Straße”. Switch to bus line 447 and get off at “Dort­mund Uni­ver­si­tät S”.

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The H-Bahn is one of the hallmarks of TU Dort­mund Uni­ver­sity. There are two stations on North Cam­pus. One (“Dort­mund Uni­ver­si­tät S”) is directly located at the suburban train stop, which connects the uni­ver­si­ty directly with the city of Dort­mund and the rest of the Ruhr Area. Also from this station, there are connections to the “Technologiepark” and (via South Cam­pus) Eichlinghofen. The other station is located at the dining hall at North Cam­pus and offers a direct connection to South Cam­pus every five minutes.

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