title: The chromatin remodeling factor CHD5 is a transcriptional repressor of WEE1.
abstract: Loss of the chromatin remodeling ATPase CHD5 has been linked to the progression of neuroblastoma tumors, yet the underlying mechanisms behind the tumor suppressor role of CHD5 are unknown. In this study, we purified the human CHD5 complex and found that CHD5 is a component of the full NuRD transcriptional repressor complex, which also contains methyl-CpG binding proteins and histone deacetylases. The CHD5/NuRD complex appears mutually exclusive with the related CHD4/NuRD complex as overexpression of CHD5 results in loss of the CHD4 protein in cells. Following a search for genes that are regulated by CHD5 in neuroblastoma cells, we found that CHD5 binds to and represses the G2/M checkpoint gene WEE1. Reintroduction of CHD5 into neuroblastoma cells represses WEE1 expression, demonstrating that CHD5 can function as a repressor in cells. A catalytically inactive mutant version of CHD5 is able to associate with a NuRD cofactor but fails to repress transcription. Our study shows that CHD5 is a NuRD-associated transcriptional repressor and identifies WEE1 as one of the CHD5-regulated genes that may link CHD5 to tumor suppression.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Quan
authors.affiliation: Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America; Blais Proteomics Center, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Adelmant
authors.affiliation: Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America; Blais Proteomics Center, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Marto
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Timur
authors.initials: T
authors.lastname: Yusufzai
mesh_terms: D000429:Alcohol Oxidoreductases; D015820:Cadherins / Q000378:metabolism; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C083970:R-cadherin; D012097:Repressor Proteins; D000429:Alcohol Oxidoreductases; C021496:lactate-malate transhydrogenase; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D004265:DNA Helicases; C471926:CHD5 protein, human