1. Chromosomes and Gene Expression
Download icon

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

  1. Luke Isbel
  2. Lexie Prokopuk
  3. Haoyu Wu
  4. Lucia Daxinger
  5. Harald Oey
  6. Alex Spurling
  7. Adam J Lawther
  8. Matthew W Hale
  9. Emma Whitelaw  Is a corresponding author
  1. La Trobe Institute for Molecular Science, Australia
  2. Hudson Institute of Medical Research, Australia
  3. Leiden University Medical Centre, Netherlands
  4. University of Queensland Diamantina Institute, Australia
  5. La Trobe University, Australia
Research Article
  • Cited 11
  • Views 1,745
  • Annotations
Cite this article as: eLife 2016;5:e15082 doi: 10.7554/eLife.15082

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.

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5270-4347
  2. Lexie Prokopuk

    Centre for Genetic Diseases, Hudson Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Haoyu Wu

    Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. 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.
  5. Harald Oey

    Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4368-6191
  7. Adam J Lawther

    Department of Psychology and Counselling, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Matthew W Hale

    Department of Psychology and Counselling, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2320-2903

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.

Reviewing Editor

  1. Anne C Ferguson-Smith, University of Cambridge, United Kingdom

Publication history

  1. Received: February 8, 2016
  2. Accepted: July 9, 2016
  3. Accepted Manuscript published: July 13, 2016 (version 1)
  4. 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.

Metrics

  • 1,745
    Page views
  • 465
    Downloads
  • 11
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology
    Michael Roland Wolff et al.
    Research Article

    Chromatin dynamics are mediated by remodeling enzymes and play crucial roles in gene regulation, as established in a paradigmatic model, the S. cerevisiae PHO5 promoter. However, effective nucleosome dynamics, i.e. trajectories of promoter nucleosome configurations, remain elusive. Here, we infer such dynamics from the integration of published single-molecule data capturing multi-nucleosome configurations for repressed to fully active PHO5 promoter states with other existing histone turnover and new chromatin accessibility data. We devised and systematically investigated a new class of 'regulated on-off-slide' models simulating global and local nucleosome (dis)assembly and sliding. Only seven of 68145 models agreed well with all data. All seven models involve sliding and the known central role of the N-2 nucleosome, but regulate promoter state transitions by modulating just one assembly rather than disassembly process. This is consistent with but challenges common interpretations of previous observations at the PHO5 promoter and suggests chromatin opening by binding competition.

    1. Chromosomes and Gene Expression
    Siheng Xiang, Douglas Koshland
    Research Article Updated

    Cohesin helps mediate sister chromatid cohesion, chromosome condensation, DNA repair, and transcription regulation. We exploited proximity-dependent labeling to define the in vivo interactions of cohesin domains with DNA or with other cohesin domains that lie within the same or in different cohesin complexes. Our results suggest that both cohesin's head and hinge domains are proximal to DNA, and cohesin structure is dynamic with differential folding of its coiled coil regions to generate butterfly confirmations. This method also reveals that cohesins form ordered clusters on and off DNA. The levels of cohesin clusters and their distribution on chromosomes are cell cycle-regulated. Cohesin clustering is likely necessary for cohesion maintenance because clustering and maintenance uniquely require the same subset of cohesin domains and the auxiliary cohesin factor Pds5p. These conclusions provide important new mechanistic and biological insights into the architecture of the cohesin complex, cohesin–cohesin interactions, and cohesin's tethering and loop-extruding activities.