Understanding the role of the histone modifier SETD2 and histone variant H3.3 in chromatin regulation and beyond

In eukaryotic cells, genomic DNA is wrapped around histone proteins to form chromatin. All processes that involve genomic DNA, including transcription, DNA replication and DNA repair, are regulated by chromatin. Two important layers of chromatin regulation are the deposition of so-called histone variants and the post-translational modification of histone proteins. In this thesis, we focus on the histone variant H3.3, which can be deposited into chromatin independent of DNA replication, and on the histone modifier SETD2, which is a conserved enzyme that methylates histone H3 on lysine 36. We focus specifically on the role of H3.3 and SETD2 in transcription regulation and histone dynamics, and also uncover an unexpected role of SETD2 in cell size control. Furthermore, we develop new technologies to study chromatin regulators in high throughput in the model organism Saccharomyces cerevisiae (budding yeast), and also start the development of similar strategies to uncover chromatin regulators in an unbiased manner in human cells.