Our group has continued studies of chromatin structure and the regulation of heat shock gene expression, with emphasis on the structure and function of the heat shock transcription factor (HSF) and on the remodeling of the heat shock gene promoter in chromatin. Yeast two- hybrid screens have been conducted to identify interacting proteins for Drosophila HSF. Biophysical studies of HSF oligomerization have determined the equilibrium dissociation constants for the monomer-trimer transition, the first step of HSF activation by heat shock. These studies show that temperature does not affect HSF trimerization directly, but through other pathways, which are currently being explored. Our group has also continued work on the ATP-dependent nucleosome remodeling factor (NURF) discovered in this laboratory. The flexible histone tails, especially those of histone H3 and H4 were found to be involved in stimulating the ATPase activity of NURF. Three out of four subunits of NURF have been identified and are currently being characterized. Using highly purified NURF, the Laboratory showed that NURF is capable of facilitating transcriptional activation on a reconstituted nucleosomal template. This demonstration shows for the first time that the direct action of a nuclesome remodeling factor is crucial for activating gene transcription under conditions that closely mimic those inside the cell, and provides clear and substantial support for the significance of this new family of transcriptional facilitators generally termed """"""""chromatin remodelers"""""""" in regulating genetic activity in health and disease.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Special Emphasis Panel (LMCB)
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National Cancer Institute Division of Basic Sciences
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Kwon, So Yeon; Xiao, Hua; Wu, Carl et al. (2009) Alternative splicing of NURF301 generates distinct NURF chromatin remodeling complexes with altered modified histone binding specificities. PLoS Genet 5:e1000574
Wu, Wei-Hua; Wu, Chwen-Huey; Ladurner, Andreas et al. (2009) N terminus of Swr1 binds to histone H2AZ and provides a platform for subunit assembly in the chromatin remodeling complex. J Biol Chem 284:6200-7
Luk, Ed; Vu, Ngoc-Diep; Patteson, Kem et al. (2007) Chz1, a nuclear chaperone for histone H2AZ. Mol Cell 25:357-68
Mizuguchi, Gaku; Xiao, Hua; Wisniewski, Jan et al. (2007) Nonhistone Scm3 and histones CenH3-H4 assemble the core of centromere-specific nucleosomes. Cell 129:1153-64
Schwanbeck, Ralf; Xiao, Hua; Wu, Carl (2004) Spatial contacts and nucleosome step movements induced by the NURF chromatin remodeling complex. J Biol Chem 279:39933-41
Mizuguchi, Gaku; Shen, Xuetong; Landry, Joe et al. (2004) ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science 303:343-8
Shen, Xuetong; Xiao, Hua; Ranallo, Ryan et al. (2003) Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates. Science 299:112-4
Shen, Xuetong; Ranallo, Ryan; Choi, Eugene et al. (2003) Involvement of actin-related proteins in ATP-dependent chromatin remodeling. Mol Cell 12:147-55