Atlas of the chromatin landscape in the developing nervous system of Drosophila melanogaster - ChIPseq and ATACseq - time series of tissue specific neuroblast histone PTMs

In this study, I identify novel regulatory nodes and potential signal transduction pathways that govern neurogenic tissue specification and differentiation. The Drosophila melanogaster central nervous system develops from three columns of neuroectodermal cells that give rise to neural stem cells called neuroblasts. I investigated the genomic regulatory state of cells derived from the ventral column (VC) and the intermediate column (IC) of the neurectoderm (NE) as they specify, diversify and differentiate. In this thesis I investigated how cell populations become distinct from one another, and how the genomic regulatory state within these cell populations changes over developmental time. As post-translational histone modification occupancy and chromatin accessibility has been linked to distinct aspects of gene regulation, I assessed their tissue specific genome wide distributions and used them as a proxy to investigate the genomic regulatory state in a developing embryo. Differential peak calling, differential enrichment analysis and machine learning was employed to identify spatiotemporally regulated cis- regulatory modules (CRMs) and differentially regulated genes (DRGs). I could show that I can accurately predict tissue specific CRMs by validating a subset of de novo predicted differentially regulated CRMs with reporter lines. The spatiotemporal regulatory trajectory of differentially regulated elements was used to refine the existing models for the gene regulatory networks that govern neuronal differentiation, to associate distal regulatory elements with core promoters, and to identify enriched sequence motifs within active CRMs. Taken together the datasets and algorithms in this study provide a comprehensive atlas of novel CRMs of the developing nervous system in Drosophila, novel insights into the regulatory nodes and edges during neurogenesis and a valuable resource to refine existing models of neurogenesis specifically and tissue differentiation generally.