| Atrophin is a little studied transcriptional corepressor that is essential during development. Mutations in the human homolog of Atrophin, Atrophin1, cause dentaorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants cause diverse phenotypes, including neurodegeneration, segmentation, patterning, and planar polarity defects. Although mutations of Atro cause a wide range of phenotypes, little is known about the binding partners and the downstream targets of Atro. This thesis presents the first genome wide analysis of Atro using chromatin immunoprecipitation sequencing to identify direct transcriptional targets of Atro. I found 1300 unique potential targets of Atro and showed Atro is required for the regulation of engrailed expression and the regulation of Decapentaplegic and Notch signaling pathways during larval development. Using bioinformatics and biochemical approaches, we showed that Atro functions with the Drosophila GAGA factor, Trithorax-like, to moderate gene expression. In addition to analyzing Atro function, the role of JAK/STAT signaling in planar polarity was investigated and I found CG14598, a secreted protein and a potential target of JAK/STAT signaling, plays a role in planar polarity. |
