Transcription repression is essential for establishing precise patterns of gene expression during development. Studies of Drosophila transcriptional regulation reveal that transcriptional repressors fall into two classes: those acting locally as "short-range" repressors, and those acting dominantly as "long-range" repressors. The types of transcription factors and cofactors involved are highly conserved in all metazoans. One area in which our knowledge has lagged is in understanding how these different classes of repressors function at a mechanistic level. Understanding of repression mechanisms in the developmental circuits will shed light on key biological processes including stem cell reprogramming, cancer, and development.In this work, I describe studies that reveal molecular mechanisms of long- and short-range repression during early Drosophila development. My chromatin studies of the prototypic long-range repressor Hairy and the short-range repressor Knirps suggest that these two modes of repression induce distinct chromatin states on the repressed genes. These results indicate that transcriptoinal corepressors can be deployed in a context-dependent manner to effect transcription. To discern the importance of individual corepressors, my studies have also examined the role of the conserved Groucho corepressor in Hairy-mediated long-range repression.
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