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Complex chromatin systems in the test tube

Final Activity Report Summary - CHROMA (Complex chromatin systems in the test tube)

In all cells of our bodies DNA complex basic proteins can be found, the so-called histones. These highly conserved proteins not only organise and protect the genetic information, but are also crucially involved in all biological processes involving DNA. In this aspect, a large number of different post-translational histone modifications direct the availability and accessibility of the DNA. While many histone modifications could be linked to different biological phenomena and signal transduction pathways, the molecular working mechanisms of most histone modifications are still not understood.

In the CHROMA research project recombinant test tube systems for the analysis of chromatin regulatory pathways could be established. Based on defined components the researchers have set up small elements of chromatin containing chemically defined histone modifications. Using sophisticated biochemical and biophysical assay systems the functional properties of the artificial chromatin elements could be defined. In particular, the researchers could characterize the working mechanism of several different proteins that interact and thereby read-out distinct histone modifications. Further, it could be shown that recruitment of different factors in dependence of distinct histone modifications to the artificial chromatin changes its overall conformation and structure.

It is proposed that such changes have profound effects onto the functional properties of the underlying DNA elements thereby controlling the functionality of the genome. Overall, the studies have likely far-reaching implications for our understanding of epigenetic regulatory mechanisms that is pathways that result in inheritable changes in gene expression profiles without changes of the DNA sequence or content. It is thought that many diseases and especially cancer have epigenetic components.