Characterizing the Nematode Dosage Compensation Complex

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DESCRIPTION (provided by applicant): To compensate for having two X chromosomes, C. elegans hermaphrodites repress transcription from both Xs by a factor of two. The Meyer lab has used a variety of cytological, biochemical, and genetic methods to show that the Dosage Compensation Complex (DCC) is important in this process. I plan to determine the mechanism of action of this Condensin-like DCC by purifying it to determine its size, composition, and DNA binding ability. The downstream effect of the complex will be investigated by determining the nature of DCC binding to DNA. Aim 2 will use a genetic screen to determine what components are required for the dosage compensation complex to spread along the X chromosome. The purpose of both sets of experiments is to understand how the additional layer of precise transcriptional regulation supplied by the dosage compensation machinery can be superimposed on the general transcription machinery. This understanding will help establish how a Condensin-like protein complex binds DNA to establish and maintain a stably inherited specialized chromatin state.