Coordinate gene regulation is a fundamental process essential to all cells from the germ line to the immune system. Our long-term goal is to define how genes are identified for coordinate regulation, the key initial step in their regulation. Dosage compensation is one of the best model systems for studying this process because all of the genes on a single chromosome are specifically identified and co-regulated. Drosophila, like mammals, increase the transcript levels of a large number of diversely-regulated genes along the length of the single male X-chromosome precisely two-fold relative to each female X-chromosome.
We are developing innovative approaches to understanding how dosage compensation in Drosophila is established, the critical first step in coordinate regulation. In this way, we will address the following key overall question: How are global and gene-specific transcriptional regulatory signals integrated to precisely regulate genes? By combining genetic, biochemical, and genomic approaches, we are addressing the following fundamental questions: 1) How are the functions of non-coding RNAs and cis-acting sequences integrated?; 2) How do multiple chromatin marks act together during targeting of transcription complexes?; 3) How can local enrichment of a DNA sequence generate a sub-nuclear domain?