Chromatin Remodeling and Transcription Repression

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DESCRIPTION (provided by applicant): ATP-dependent chromatin remodeling is involved in the regulation of transcription, DNA replication, recombination, and DNA repair. Often this kind of chromatin remodeling is associated with making the DNA more accessible to other DNA-binding factors thereby promoting their binding to specific target sites. One class of ATP-dependent chromatin remodeling complexes, referred to as imitation switch (ISWI) family, has the general properties of globally regulating chromatin structure, forming repressive chromatin structures, and of being involved in transcription repression. In Saccharomyces cerevisiae there are two ISWl like genes, namely ISW1 and ISW2. The Isw1p protein is assembled into two distinct complexes referred to as ISW1a and ISW1b; whereas only one complex of ISW2 is found. ISW2 has been shown to be required for repression of meiotic genes and to be recruited by the Ume6 repressor protein. ISW1a/b have also been recently shown to be involved in transcription termination. It is not clear yet how these complexes remodel nucleosomes and what the net structural changes caused in chromatin. Results from our lab and those of Peter Becker have shown that ISWI remodeling does not change the canonical nucleosome structure and yet it is also clear that these do promote the formation of a more condensed chromatin fiber structure. Our proposal is to determine how ISW2 and ISW1 bind to nucleosomes, what are the structural intermediates involved in remodeling, and how do these changes affect the higher ordered structure of chromatin.