The body contains hundreds of cell types that greatly differ in morphology and function, such as embryonic and adult stem cells, differentiated and specialised cells and non-dividing differentiated cells. Chromatin changes mediate differentiation, whereas erroneous changes may give rise to the formation of tumours.
Cells use several, tightly integrated strategies to bring about changes in chromatin at different levels of chromatin organisation, such as the action of DNA-binding proteins (transcription factors), enzymatic histone modification and nucleosome positioning. Furthermore, larger chromatin domains are established that contain several co-regulated genes. Such genes can be arranged in clusters along the DNA, they can reside in the same "chromatin loop" or, genes located at distant genomic loci (and even different chromosomes), can come together in large nuclear assemblies, such as "transcription factories". Coordinated chromatin-mediated gene regulation can span whole chromosomes, as in case of X inactivation, and can even include the entire genome, as observed during spermatogenesis. All of these are not independent processes, but rather are tightly interconnected. Therefore, to better understand chromatin changes during differentiation and malignancy, an integrated approach is required, which simultaneously considers these different levels of chromatin regulation.
The TRR81 is a unique instrument to host a large number of state-of-the-art methods required to bridge local chromatin changes mediated by transcription factors, enzymatic modifications and long-range chromatin interactions of the genome in nuclear space. It represents an integrated approach to investigate the many interdependent mechanisms that underlie chromatin changes during normal differentiation and disease.
Cover art: BBA-Molecular Cell Research, Vol. 1783, Issue 11