An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

Chromatin architecture and epigenetic signatures are fundamental players in nuclear processes such as gene regulation and genomic integrity. We are using the nucleolus as a model to investigate how specific chromatin and epigenetic states are established and maintained during cell division and how these signatures exert their function in gene expression and nuclear architecture. The nucleolus contains hundreds of ribosomal RNA (rRNA) genes that share the same sequences but display different functions (active/silent) and distinct chromatin and epigenetic features (euchromatic/heterochromatic). Thus, the systematic analysis of the nucleolus has the potential to elucidate basic mechanisms that signal and impose specific chromatin and epigenetic states independently of sequences and cellular localization. We discovered key-regulators of rDNA heterochromatin and highlighted nucleolar heterochromatin as an important component of nuclear architecture, implicated in stability, organization and chromatin features of heterochromatic repeats located outside the nucleolus. Currently, we are profiling the dynamic interplay and relationship between nucleolar and nuclear heterochromatic regions under defined transition states which we analyze by affecting key components of nucleolar heterochromatin and by using genome-wide and proteomic approach as well as fluorescence imaging and biochemical reconstitution.

Lab members involved:

• Natasa Savic – PhD student
• Eva Vollenweider – PhD student
• Sandra Frommel– PhD student
• Sergio Leone – PhD student
• Cristina Gerig – Master student
• Dominik Bär – technician