News

25.04.2017

T cell response in time resolution

Researchers at the Helmholtz Zentrum München have stimulated T cells and display a temporal breakdown of the global genetic activity. According to their article in ‘Cell Reports’, they used a number of methods to examine the entire process, from the DNA reading through to the production of the finished proteins.

Dr. Johannes Lichti, Dr. Elke Glasmacher, Dr. Kathrin Davari (from left). Source: HMGU

When it is time for the immune system to act, it often must do so very rapidly. Within the shortest time, the affected cells shift their genetic activities and adapt to the new situation. This also affects the T cells (T lymphocytes), a sub-group of the white blood cells. “But until now, it was not known which genes come into play at exactly what time,” explains Dr. Elke Glasmacher, group leader at the Institute for Diabetes and Obesity (IDO).

She and her team therefore examined T cell activation with various methods* and at defined time intervals. “Thanks to the combination of a number of techniques and the exact temporal breakdown, we were able to describe the dynamics of roughly 10,000 genes,” the study leader says. This ranged from binding the reading polymerase, to changing the reading rate, to the splicing and finally the translation of the genetic information into proteins. The key result of the study, which was carried out by Kathrin Davari and Dr. Johannes Lichti (both IDO), is that rapid de novo binding of RNA Polymerase II is responsible for almost all changes in the activated T cells.

“The study is a good basis for T cell biologists because it provides an overview of all affected genes,” explains Glasmacher. “It also generated interesting findings in the area of epigenetics.” Unlike what was previously assumed, it was seen that fast binding of the polymerase to the gene is responsible for most of the changes. According to the authors, changes in transcription resulted immediately in translation for more than 90 percent of the genes regulated. The researchers were furthermore able to show that the so-called cotranscriptional splicing, or trimming of the messenger RNA, slowed down at the beginning of the T cell response.  

“At this time it is still not clear if this is only a result of the RNA Polymerase II reorientation or if it has functional significance that is important for the T cells; this will be a part of future work”, Glasmacher states.

Further information

* 4sU-Seq, RNA-Seq, ribosome profiling und RNA polymerase II (RNAPII) ChIP-Seq

Publication:
Davari, K. & Lichti, J. et al. (2017): Rapid Genome-wide Recruitment of RNA Polymerase II Drives Transcription, Splicing and Translation Events during T Cell Responses. Cell Reports, DOI: http://dx.doi.org/10.1016/j.celrep.2017.03.069, Abstract...

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute of Diabetes and Obesity (IDO) studies the diseases of the metabolic syndrome by means of systems biological and translational approaches on the basis of cellular systems, genetically modified mouse models and clinical intervention studies. It seeks to discover new signaling pathways in order to develop innovative therapeutic approaches for the personalized prevention and treatment of obesity, diabetes and their concomitant diseases. IDO is part of the Helmholtz Diabetes Center (HDC).