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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM070864-02
Application #
6867294
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Carter, Anthony D
Project Start
2004-04-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
2
Fiscal Year
2005
Total Cost
$221,650
Indirect Cost
Name
Southern Illinois University Carbondale
Department
Biochemistry
Type
Schools of Medicine
DUNS #
939007555
City
Carbondale
State
IL
Country
United States
Zip Code
62901
Bartholomew, Blaine (2014) ISWI chromatin remodeling: one primary actor or a coordinated effort? Curr Opin Struct Biol 24:150-5
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Deindl, Sebastian; Hwang, William L; Hota, Swetansu K et al. (2013) ISWI remodelers slide nucleosomes with coordinated multi-base-pair entry steps and single-base-pair exit steps. Cell 152:442-52
Hota, Swetansu K; Bhardwaj, Saurabh K; Deindl, Sebastian et al. (2013) Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains. Nat Struct Mol Biol 20:222-9
Dechassa, Mekonnen Lemma; Hota, Swetansu K; Sen, Payel et al. (2012) Disparity in the DNA translocase domains of SWI/SNF and ISW2. Nucleic Acids Res 40:4412-21
Hota, Swetansu K; Bartholomew, Blaine (2011) Diversity of operation in ATP-dependent chromatin remodelers. Biochim Biophys Acta 1809:476-87
Gaykalova, Daria A; Nagarajavel, V; Bondarenko, Vladimir A et al. (2011) A polar barrier to transcription can be circumvented by remodeler-induced nucleosome translocation. Nucleic Acids Res 39:3520-8
Gangaraju, Vamsi K; Prasad, Punit; Srour, Ali et al. (2009) Conformational changes associated with template commitment in ATP-dependent chromatin remodeling by ISW2. Mol Cell 35:58-69
Gangaraju, Vamsi K; Bartholomew, Blaine (2007) Mechanisms of ATP dependent chromatin remodeling. Mutat Res 618:3-17
Dang, Weiwei; Bartholomew, Blaine (2007) Domain architecture of the catalytic subunit in the ISW2-nucleosome complex. Mol Cell Biol 27:8306-17

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