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Advances in Epigenome Research

Collective publication by the International Human Epigenome Consortium with contributions by the Kiel-based working groups from the Cluster of Excellence "Inflammation at Interfaces"

The global research consortium IHEC (International Human Epigenome Consortium) is now publishing a collection of 41 works in renowned research journals. Scientists from Kiel also form part of the consortium, which researches fundamental processes that turn genes on and off in cells and therefore regulate how the cells specialise, how they control functions or how diseases come about. With significant support from Kiel, new findings have been made about highly specialised cells of the immune system, the T cells.  "We now understand how a memory is programmed in the genetic make-up of the immune cells and why the cells can react much more quickly and more effectively when they come into contact with a pathogen again", explains Professor Philip Rosenstiel of the Schleswig-Holstein-based Cluster of Excellence "Inflammation at Interfaces". Rosenstiel and his team from the Institute of Clinical Molecular Biology at Kiel University's Faculty of Medicine have specialised in analysing the transcriptome. The transcriptome, which is all of the gene readouts in a cell, reflects the activity of the gene expression in a cell. The results of the study on memory formation by T cells will now be published in the specialist journal Immunity. Acting as a cooperation partner in this was a working group from the German Rheumatism Research Centre Berlin.

How are genes switched on and off in cells? Put simply, this is the question that epigenetics deals with. In order to understand how cells specialise, how bodily functions are controlled or how diseases come about, decoding the genome, or knowing the building block sequence of the individual gene is simply not enough. The state of activity of the gene is also important, and this is essentially determined by small chemical changes in the genetic material, known as epigenetic markers. Epigenetic control elements include, for example, DNA methylation. This is when a methyl group is added to a DNA building block. By doing so, regulatory sequences are basically sealed off, which means the machinery that reads the gene is no longer able to bind to the DNA and so the gene cannot become active. Another chemical modification relates to DNA packaging. In simple terms, a gene can be read if the DNA is loosely packaged, otherwise it probably cannot be read.

This and other chemical DNA modifications have been systematically recorded, worldwide, since 2010 in the International Human Epigenome Consortium (IHEC). This major project aims to produce the epigenetic profile of every type of human cell. These reference epigenomes should then be publicly available, so that they can act as comparative data for future research projects. Two working groups from Kiel are involved in the German part of the IHEC, the Deutsches Epigenom Programm, DEEP. These groups are addressing the epigenetic modifications in chronic inflammatory bowel diseases (headed by: Professor Stefan Schreiber, spokesperson for the Cluster of Excellence "Inflammation at Interfaces") and the analysis of the transcriptome (headed by: Professor Philip Rosenstiel).

Current findings in the IHEC epigenome research will now be published in a comprehensive collection of 41 articles in total, including 4 from German partners of the consortium. The publications illuminate different aspects of epigenetic control in human body cells. “The knowledge gained is comparable to that of the 1000 Genomes Project, in which the genomes from around 2,500 people were sequenced and used to compile a detailed catalogue of human genetic variations,” stated Cluster Board Member, Professor Philip Rosenstiel.

Rosenstiel and his team were involved as a cooperation partner in a study  which recorded the entire epigenetic network of long-lasting T cells for the first time. These highly specialised cells of the immune system are, on the one hand, essential for fighting off pathogens, but on the other hand, also cause autoimmune diseases if the body’s own control mechanisms fail. In the published project, research was carried out into how the epigenome contributes towards the formation, stability and function of various development stages of the T cells. In the world’s most comprehensive data set on these cells, they were able to record genome-wide and gene-specific changes and their functional consequences. Using this data, it was also possible to identify brand new factors, in addition to the known regulators, which are important for developing memory cells in the blood of healthy people. At the same time, they form the basis for identifying critical epigenetic changes in T cells which occur in chronic inflammatory and autoimmune diseases, and can be decisive for the course of the disease and the success of treatment.


The official English IHEC press release on publishing the collection can be retrieved at: http://ihec-epigenomes.org/news-events/coordinatedpaper-release

The full collection of IHEC publications can be retrieved at:
http://www.cell.com/consortium/IHEC


Philip Rosenstiel, Cluster of Excellence "Inflammation at Interfaces", Professor of Molecular Medicine at Kiel University and Director of the Institute of Clinical Molecular Biology at Kiel University's Faculty of Medicine and University Medical Center Schleswig-Holstein (UKSH), Campus Kiel. Photo: Dr. Tebke Böschen/ Kiel University


Contact:
Prof. Dr. Philip Rosenstiel
The Institute of Clinical Molecular Biology
Tel.: +49 (0)431 500 15105
p.rosenstiel@mucosa.de

Cluster of Excellence "Inflammation at Interfaces"
Scientific Office, Head: Dr. habil. Susanne Holstein
Press and Communications, Sonja Petermann, Text: Kerstin Nees
Postal address: Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Tel.: +49 (0)431 880-4850, Fax: +49 (0)431 880-4894
E-mail: spetermann@uv.uni-kiel.de
Website: www.inflammation-at-interfaces.de


The Cluster of Excellence "Inflammation at Interfaces" has been funded since 2007 by the Excellence Initiative of the German Government and the federal states with a total budget of 68 million Euros. It is currently in its second phase of funding. Around 300 cluster members are spread across the four locations: Kiel (Kiel University, University Medical Center Schleswig-Holstein (UKSH)), Lübeck (University of Lübeck, UKSH), Plön (Max Planck Institute for Evolutionary Biology) and Borstel (Research Center Borstel (FZB) – Center for Medicine and Biosciences) and are researching an innovative, systematic approach to the phenomenon of inflammation, which can affect all barrier organs such as the intestines, lungs and skin.

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