title: Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse.
abstract: We previously identified Wiz in a mouse screen for epigenetic modifiers. Due to its known association with G9a/GLP, Wiz is generally considered a transcriptional repressor. Here, we provide evidence that it may also function as a transcriptional activator. Wiz levels are high in the brain, but its function and direct targets are unknown. ChIP-seq was performed in adult cerebellum and Wiz peaks were found at promoters and transcription factor CTCF binding sites. RNA-seq in Wiz mutant mice identified genes differentially regulated in adult cerebellum and embryonic brain. In embryonic brain most decreased in expression and included clustered protocadherin genes. These also decreased in adult cerebellum and showed strong Wiz ChIP-seq enrichment. Because a precise pattern of protocadherin gene expression is required for neuronal development, behavioural tests were carried out on mutant mice, revealing an anxiety-like phenotype. This is the first evidence of a role for Wiz in neural function.
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.
authors.forename: Luke
authors.identifier: 0000-0002-5270-4347
authors.initials: L
authors.lastname: Isbel
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.
authors.forename: Lexie
authors.initials: L
authors.lastname: Prokopuk
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.|Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Lucia
authors.initials: L
authors.lastname: Daxinger
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.
authors.forename: Harald
authors.initials: H
authors.lastname: Oey
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.
authors.forename: Alex
authors.identifier: 0000-0002-4368-6191
authors.initials: A
authors.lastname: Spurling
authors.affiliation: Department of Psychology and Counselling, La Trobe University, Melbourne, Australia.|School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Lawther
authors.affiliation: Department of Psychology and Counselling, La Trobe University, Melbourne, Australia.|School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hale
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.
authors.forename: Emma
authors.identifier: 0000-0002-2320-2903
authors.initials: E
authors.lastname: Whitelaw
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001665:Binding Sites; D000076246:CCCTC-Binding Factor / Q000378:metabolism*; D002531:Cerebellum / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017422:Sequence Analysis, DNA
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C119196:Wiz protein, mouse
keywords: chromosomes; epigenetics; genes; momme; mouse; widely interspaced zinc finger motifs