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A multitude of DNA sequence-dependent and -independent interactions coordinate the spatiotemporal recruitment of regulatory proteins to the genome. Interference or lack of specificity in this process results in defective embryonic development and can give rise to various human diseases, including cancer. We are interested to uncover the rules that specify such protein-genome interactions.

The mammalian genome is packaged into chromatin, with nucleosomes as the basic subunit. Chemical modifications of chromatin serve as interaction hubs for many nuclear proteins. The precise deposition, removal, and maintenance of chromatin marks along the genome relies on coordinated activities of writer, eraser, and reader enzymes. However, how these regulators are recruited to the correct genomic coordinates and at the right time, is not fully understood. Uncovering the mechanisms underlying this coordination is an important step towards understanding how chromatin influences important biological processes, including DNA replication, transcription, genome organization, and DNA damage repair.

We combine various experimental and computational strategies to understand the fundamental processes underlying precise protein-chromatin interactions. Methodologies include genome and epigenome engineering, genome-wide studies, proteomics, single-cell measurements, and computational modelling. We use mouse embryonic stem cells and their differentiation to neuronal and haematopoietic cells as our main model system.