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Koenecke, Nina
(2015).
DOI: https://doi.org/10.21954/ou.ro.0000f86e
Abstract
Transcriptional enhancers drive tissue-specific gene regulation of their target genes, but it is challenging to identify tissue-specific enhancers and determine their activity during development. Is the enhancer activating or repressing their target gene and in which tissue does this happen? In this thesis I aim to identify markers for tissue-specific enhancer activity. We investi-gate ChIP-seq binding profiles of transcription factors, co-regulators, and histone modifica-tions at known DV enhancers during the patterning of the Dorsal-Ventral (DV) axis in Drosophila melanogaster embryogenesis. We utilize Drosophila mutant embryos that consist homogenously of precursor cells for either the mesoderm or dorsal ectoderm, which allows us to compare ChIP-seq binding profiles at known DV enhancers between two separate DV tis-sues. Our results show that transcription factors are recruited more strongly to known DV enhancers in the tissue they are active in, than in the tissue that they are repressed in. This preference for active enhancers is also shown by co-regulators, which are recruited by tran-scription factors and co-regulate transcription. We find that histone modifications are good markers for enhancer activity of known DV enhancers. The active mark H3K27ac and the gen-eral mark H3K4me1 mark active tissue-specific enhancers, while the silenced H3K27me3 marks spatially repressed DV enhancers during DV patterning. We also show that known DV enhancers are not poised for future activation; rather, DV enhancers with H3K27me3 are re-pressed longer during embryo development. We utilize differential H3K27ac levels between tissues to identify putative tissue-specific DV enhancers and show that they are functional DV enhancers that drive expression in a DV manner and are close to differentially expressed genes between DV mutants. In conclusion, we find that histone modifications are good markers for tissue-specific enhancer activity during patterning and analysis of differential H3K27ac levels between tissues can identify putative functional tissue-specific enhancers during DV patterning.