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Title
Japanese: 
English:HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome 
Author
Japanese: Jenness C., Giunta S., Muller M. M., 木村 宏, Muir T. W., Funabiki H..  
English: C. Jenness, S. Giunta, M. M. Muller, H. Kimura, T. W. Muir, H. Funabiki.  
Language English 
Journal/Book name
Japanese: 
English:Proceedings of the National Academy of Sciences of the United States of America 
Volume, Number, Page        
Published date Jan. 16, 2018 
Publisher
Japanese: 
English: 
Conference name
Japanese: 
English: 
Conference site
Japanese: 
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DOI https://doi.org/10.1073/pnas.1717509115
Abstract Mutations in CDCA7, the SNF2 family protein HELLS (LSH), or the DNA methyltransferase DNMT3b cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. While it has been speculated that DNA methylation defects cause this disease, little is known about the molecular function of CDCA7 and its functional relationship to HELLS and DNMT3b. Systematic analysis of how the cell cycle, H3K9 methylation, and the mitotic kinase Aurora B affect proteomic profiles of chromatin in Xenopus egg extracts revealed that HELLS and CDCA7 form a stoichiometric complex on chromatin, in a manner sensitive to Aurora B. Although HELLS alone fails to remodel nucleosomes, we demonstrate that the HELLS-CDCA7 complex possesses nucleosome remodeling activity. Furthermore, CDCA7 is essential for loading HELLS onto chromatin, and CDCA7 harboring patient ICF mutations fails to recruit the complex to chromatin. Together, our study identifies a unique bipartite nucleosome remodeling complex where the functional remodeling activity is split between two proteins and thus delineates the defective pathway in ICF syndrome.

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