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Projects of the TRR 81

The projects of the TRR 81 are using multiple, complementary models to address several fundamental aspects of chromatin changes during differentiation. These models include: ES cells and cell lines that allow differentiation towards neural lineages (A03 Bauer, A09 Poot, A15N Hake, B04 Galjart, B15N Van den Berg), skeletal muscle and cardiomyocyte differentiation (A02 Braun/Yuan, B04 Galjart, Papantonis B14N), Drosophila and mouse germ cell differentiation (A01 Brehm, B09 Baarends/Houtsmuller), cells of the immune system and their activation by signalling (A12 Borggrefe, B02 Kracht, A16N Stadhouders), hematopoietic stem cells and their differentiation (A04 Philipsen/van Dijk, B01 Grosveld) as well as cancer cell lines in general and lung cancer models in particular (A10 Stiewe, A17N Liefke, B07 Dobreva). The central projects Z01 and Z04N support projects working on all model systems.
Photo: Alexander Brehm
Models used by the TRR 81 projects to analyze chromatin-based mechanisms underlying differentiation, activation, and pathological transformation.

The differentiation of cells, in both normal and disease settings, is largely governed by changes to chromatin structure. These changes, which manifest at several levels, determine gene activity and thereby the developmental program in time and space. At a more local level, genome regions containing one or several genes are embedded in a relatively open and accessible chromatin structure and are enriched for active histone marks. Others have a more closed chromatin conformation and predominantly carry repressive histone marks. Changes between these two chromatin states are largely modulated and shaped by DNA binding transcription factors targeting enzymatic functions, such as histone modifying and nucleosome remodelling enzymes, to chromatin. At a more global level, structural proteins such as CTCF or cohesin drive chromatin folding, loop formation, intra- and inter-chromosomal contacts to regulate accessibility and activity of larger genomic regions.

A chromosome is enlarged in multiple steps depicting the compacted chromatin fibre, the loosened DNA strand wrapped around nucleosomes, and finally the DNA double helix.

These two modes of chromatin regulation (local and global) are tightly interconnected but serve as a conceptual framework to divide the projects of the TRR81 into two groups: "A projects" focus on transcription factor and enzyme-driven chromatin changes and "B projects" study the genomic organisation in nuclear space.