Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse

Abstract
Data availability
Article and author information
Metrics

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

The following data sets were generated

1. Isbel L
2. Prokopuk L
3. Daxinger L
4. Oey H
5. Spurling A
6. Lawther A
7. Hale M
8. Whitelaw E
(2016) Widely Interspaced Zinc Finger Motifs, Wiz, binds promoters containing CTCF-binding sites and is required for normal neural function in the mouse
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE76909).

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=gvevucmozpevpsl&acc=GSE76909

The following previously published data sets were used

1. Bian C
2. Chen Q
3. Yu X
(2015) G9a, ZNF644 and WIZ ChIP-seq results
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE62616).

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62616

Article and author information

Author details

Luke Isbel

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5270-4347
Lexie Prokopuk

Centre for Genetic Diseases, Hudson Institute of Medical Research, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Haoyu Wu

Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands

Competing interests
The authors declare that no competing interests exist.
Lucia Daxinger

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Harald Oey

Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, Australia

Competing interests
The authors declare that no competing interests exist.
Alex Spurling

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4368-6191
Adam J Lawther

Department of Psychology and Counselling, La Trobe University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Matthew W Hale

Department of Psychology and Counselling, La Trobe University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Emma Whitelaw

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia

For correspondence
e.whitelaw@latrobe.edu.au

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2320-2903

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

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.