Role of the histone chaperone Nap1l1 in chromatin reorganisation during reprogramming and differentiation

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The early mammalian development is characterised by profound global chromatin changes mediated by assembly/disassembly of histones and their variants. Changes of the chromatin structure affects several cellular processes such as DNA replication, transcription or repair. Histone chaperones escort histones or histone variants throughout their life and are involved in chromatin assembly/disassembly but also in the nuclear import, storage, or degradation of histones. The histone chaperone Nucleosome assembly protein 1 like 1 (Nap1l1) belongs to the Nap1 family of histone chaperones that is highly conserved throughout eukaryotes. Nap1 family members are described to mediate chromatin assembly and disassembly of H2A/H2B and their variants (e.g. H2A.X, H2A.Z, TH2B). Although there are several studies about Nap1l1 homologs in yeast, plants and flies, the role of Nap1l1 in mammalian development has remained elusive. In this project, I will elucidate the role of Nap1l1 in the dynamic distribution of histones and their variants in different stages of mouse development: 1) during the development of the pre-implantation embryo, 2) in the process of epigenetic reprogramming in primordial germ cells, 3) in pluripotent stem cells and 4) in the differentiation of male germ cells. Therefore, we will use a Nap1l1 conditional knockout mouse model to deplete Nap1l1 in the particular stages of mouse development and analyse the chromatin composition. This project is expected to reveal critical insights into the function of the histone chaperone Nap1l1 and how this protein affects chromatin reorganisation during development. A better understanding of histone chaperones and how they regulate chromatin structure during reprogramming and differentiation will contribute to the development of new applications in regenerative medicine.