Histone ubiquitination

The chromatin in eukaryotic cells plays a fundamental role in all processes during a cell’s life cycle. This nucleoprotein is normally tightly packed but needs to be unpacked for expression and division. The linker histones are critical for such packaging processes and while most experimental and simulation works recognize their crucial importance, the focus is nearly always set on the nucleosome as the basic chromatin building block. Linker histones can undergo several modifications, but only few studies on their ubiquitylation have been conducted. Mono-ubiquitylated linker histones (HUb), while poorly understood, are expected to influence DNA compaction.

With the help of advanced sampling molecular dynamics simulations dynamic data of ubiquitylated linker histones is generated. The simulations are clustered into conformationally similar (sub)-states which are then evaluated for their propensity to fit into nucleosome structures. Multiple parent chromatosomes structures can be screened with an in-home developed geometric scoring approach which also allows to make predictions for longer nucleosome arrays.