A significant biological question that needs to be understood is how ATP-dependent chromatin remodeling complexes are targeted to specific promoters. Therefore, a specific aim of this research proposal is to elucidate the molecular mechanism(s) of complex recruitment. It is rapidly becoming paramount to understand this targeting process since there has been an explosion of scientific discoveries linking altered chromatin-remodeling function with cancer. To facilitate the understanding of complex recruitment, the budding yeast, Saccharomyces cerevisiae, will be used as a model organism. Given its genetic tractability, yeast is an appealing organism with which to study the underlying molecular mechanisms of modifiers of chromatin structure. Moreover, the complete genome of S. cerevisiae has been sequenced and this allows for the ability to employ genome-wide DNA microarray technology. The preliminary data obtained by this technique will allow for the global identification of promoters associated with specific chromatin modifiers which will lead to the following question: what promoter sequences are required for recruitment of a given modifying activity? This fundamental but critical mechanistic question can be answered by promoter deletion analysis, construction of heterologous promoters, and detailed analysis of promoter chromatin structure. Once the molecular targeting of these complexes is firmly understood, future experiments can be proposed to determine the involvement of ATP-dependent chromatin remodeling complexes with cancer.
| Sekinger, Edward A; Moqtaderi, Zarmik; Struhl, Kevin (2005) Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast. Mol Cell 18:735-48 |
