Abstract

In yeast and humans, previous experiences can lead to epigenetic transcriptional memory: repressed genes that exhibit mitotically heritable changes in chromatin structure and promoter recruitment of poised RNA polymerase II preinitiation complex (RNAPII PIC), which enhances future reactivation. Here, we show that INO1 memory in yeast is initiated by binding of the Sfl1 transcription factor to the cis-acting Memory Recruitment Sequence, targeting INO1 to the nuclear periphery. Memory requires a remodeled form of the Set1/COMPASS methyltransferase lacking Spp1, which dimethylates histone H3 lysine 4 (H3K4me2). H3K4me2 recruits the SET3C complex, which plays an essential role in maintaining this mark. Finally, while active INO1 is associated with Cdk8- Mediator, during memory, Cdk8+ Mediator recruits poised RNAPII PIC lacking the Kin28 CTD kinase. Aspects of this mechanism are generalizable to yeast and conserved in human cells. Thus, COMPASS and Mediator are repurposed to promote epigenetic transcriptional poising by a highly conserved mechanism.

Article and author information

Author details

  1. Agustina D'Urso

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  2. Yoh-hei Takahashi

    Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, United States
    Competing interests
    No competing interests declared.
  3. Bin Xiong

    Department of Statistics, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  4. Jessica Marone

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  5. Robert Coukos

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  6. Carlo Randise-Hinchliff

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  7. Ji-Ping Wang

    Department of Statistics, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  8. Ali Shilatifard

    Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, United States
    Competing interests
    Ali Shilatifard, Reviewing editor, eLife.
  9. Jason H Brickner

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    For correspondence
    j-brickner@northwestern.edu
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. Alan G Hinnebusch, National Institute of Child Health and Human Development, United States

Version history

  1. Received: April 6, 2016
  2. Accepted: June 22, 2016
  3. Accepted Manuscript published: June 23, 2016 (version 1)
  4. Version of Record published: July 19, 2016 (version 2)

Copyright

© 2016, D'Urso 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

  • 5,693
    Page views
  • 1,282
    Downloads
  • 92
    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)

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

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

  1. Agustina D'Urso
  2. Yoh-hei Takahashi
  3. Bin Xiong
  4. Jessica Marone
  5. Robert Coukos
  6. Carlo Randise-Hinchliff
  7. Ji-Ping Wang
  8. Ali Shilatifard
  9. Jason H Brickner
(2016)
Set1/COMPASS and Mediator are repurposed to promote epigenetic transcriptional memory
eLife 5:e16691.
https://doi.org/10.7554/eLife.16691

Share this article

https://doi.org/10.7554/eLife.16691

Further reading

    1. Cell Biology
    Wan-ping Yang, Mei-qi Li ... Qian-qian Luo
    Research Article

    High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen’s ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

    1. Cell Biology
    Jurgen Denecke
    Insight

    Mapping proteins in and associated with the Golgi apparatus reveals how this cellular compartment emerges in budding yeast and progresses over time.