1. Genes and Chromosomes
Download icon

Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter

  1. Minghao Chia
  2. Amy Tresenrider
  3. Jingxun Chen
  4. Gianpiero Spedale
  5. Victoria Jorgensen
  6. Elçin Ünal Is a corresponding author
  7. Folkert Jacobus van Werven Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. University of California, Berkeley, United States
Research Article
Cited
0
Views
315
Comments
0
Cite as: eLife 2017;6:e27420 doi: 10.7554/eLife.27420

Abstract

Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in Saccharomyces cerevisiae, expression of the kinetochore complex subunit Ndc80 is downregulated by a 5' extended long undecoded NDC80 transcript isoform. Here we demonstrate a transcriptional interference mechanism that is responsible for inhibiting expression of the coding NDC80 mRNA isoform. Transcription from a distal NDC80 promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish a repressive chromatin state in the downstream canonical NDC80 promoter. As a consequence, NDC80 expression is repressed during meiotic prophase. The transcriptional mechanism described here is rapidly reversible, adaptable to fine-tune gene expression, and relies on Set2 and the Set3 histone deacetylase complex. Thus, expression of a 5' extended mRNA isoform causes transcriptional interference at the downstream promoter. We demonstrate that this is an effective mechanism to promote dynamic changes in gene expression during cell differentiation.

Article and author information

Author details

  1. Minghao Chia

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Amy Tresenrider

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jingxun Chen

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Gianpiero Spedale

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Victoria Jorgensen

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Elçin Ünal

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    elcin@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
  7. Folkert Jacobus van Werven

    The Francis Crick Institute, London, United Kingdom
    For correspondence
    folkert.vanwerven@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-6685-2084

Funding

Francis Crick Institute (FC001203)

  • Folkert Jacobus van Werven

Pew Charitable Trusts (27344)

  • Elçin Ünal

Glenn Foundation for Medical Research

  • Elçin Ünal

March of Dimes Foundation (5-FY15-99)

  • Elçin Ünal

National Science Foundation (DGE-1106400 Graduate Student Fellowship)

  • Jingxun Chen
  • Elçin Ünal

Agency for Science, Technology and Research (Graduate Student Fellowship)

  • Minghao Chia

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Scott Keeney, Reviewing Editor, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: April 3, 2017
  2. Accepted: September 13, 2017
  3. Accepted Manuscript published: September 14, 2017 (version 1)

Copyright

© 2017, Chia 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

  • 315
    Page views
  • 93
    Downloads
  • 0
    Citations

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

Comments

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. Neuroscience
    Hiroaki Koseki et al.
    Research Article Updated