Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse
- La Trobe Institute for Molecular Science, Australia
- Hudson Institute of Medical Research, Australia
- Leiden University Medical Centre, Netherlands
- University of Queensland Diamantina Institute, Australia
- La Trobe University, Australia
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 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.
Data availability
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Widely Interspaced Zinc Finger Motifs, Wiz, binds promoters containing CTCF-binding sites and is required for normal neural function in the mousePublicly available at the NCBI Gene Expression Omnibus (accession no: GSE76909).
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G9a, ZNF644 and WIZ ChIP-seq resultsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE62616).
Article and author information
Author details
Reviewing Editor
- Anne C Ferguson-Smith, University of Cambridge, United Kingdom
Ethics
Animal experimentation: All animal work was conducted in accordance with the Australian code for the care and use of animals for scientific purposes, this study was approved by the Animal Ethics Committee of La Trobe University, project numbers 12-74, 12-75, 15-01.
Version history
- Received: February 8, 2016
- Accepted: July 9, 2016
- Accepted Manuscript published: July 13, 2016 (version 1)
- Version of Record published: August 8, 2016 (version 2)
Copyright
© 2016, Isbel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse
eLife 5:e15082.
https://doi.org/10.7554/eLife.15082
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