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Proc Natl Acad Sci U S A 2018 Jan 30;1155:E876-E885. doi: 10.1073/pnas.1717509115.
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HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome.

Jenness C , Giunta S , Müller MM , Kimura H , Muir TW , Funabiki H .

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.

PubMed ID: 29339483
PMC ID: PMC5798369
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: atr atrip cdca7 chd1 chd2 chd3 chd4 chd5 chd6 chd7 chd8 chd9 dna2 dnmt3a etaa1 fbxl12 helb hells mbp rad17 smarca1 smarca2 smarca4 smarca5 smarcal1 suv39h1 topbp1 zbtb24
GO keywords: chromatin binding [+]

Disease Ontology terms: immunodeficiency-centromeric instability-facial anomalies syndrome

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References [+] :
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