학술논문
Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse.
Document Type
Academic Journal
Author
Isbel L; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.; Prokopuk L; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.; Wu H; Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.; Daxinger L; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.; Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.; Oey H; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.; Spurling A; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.; Lawther AJ; Department of Psychology and Counselling, La Trobe University, Melbourne, Australia.; School of Psychology and Public Health, La Trobe University, Melbourne, Australia.; Hale MW; Department of Psychology and Counselling, La Trobe University, Melbourne, Australia.; School of Psychology and Public Health, La Trobe University, Melbourne, Australia.; Whitelaw E; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia.
Source
Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
Subject
Language
English
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.