Mitotically heritable, RNA polymerase II-independent H3K4 dimethylation stimulates INO1 transcriptional memory

Abstract

For some inducible genes, the rate and molecular mechanism of transcriptional activation depends on the prior experiences of the cell. This phenomenon, called epigenetic transcriptional memory, accelerates reactivation and requires both changes in chromatin structure and recruitment of poised RNA Polymerase II (RNAPII) to the promoter. Memory of inositol starvation in budding yeast involves a positive feedback loop between transcription factor-dependent interaction with the nuclear pore complex and histone H3 lysine 4 dimethylation (H3K4me2). While H3K4me2 is essential for recruitment of RNAPII and faster reactivation, RNAPII is not required for H3K4me2. Unlike RNAPII-dependent H3K4me2 associated with transcription, RNAPII-independent H3K4me2 requires Nup100, SET3C, the Leo1 subunit of the Paf1 complex and, upon degradation of an essential transcription factor, is inherited through multiple cell cycles. The writer of this mark (COMPASS) physically interacts with the potential reader (SET3C), suggesting a molecular mechanism for the spreading and re-incorporation of H3K4me2 following DNA replication.

Data availability

The scripts used to analyze the competition experiments are available at https://github.com/jasonbrickner/SeqComp.

Article and author information

Author details

  1. Bethany Sump

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  2. Donna G Brickner

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  3. Agustina D'Urso

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    Agustina D'Urso, is affiliated with Arcturus Therapeutics. The author has no financial interests to declare.
  4. Seo Hyun Kim

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  5. Jason H Brickner

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    For correspondence
    j-brickner@northwestern.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8019-3743

Funding

National Institute of General Medical Sciences (R35 GM136419)

  • Bethany Sump
  • Donna G Brickner
  • Agustina D'Urso
  • Seo Hyun Kim
  • Jason H Brickner

National Institute of General Medical Sciences (R01 GM118712)

  • Bethany Sump
  • Donna G Brickner
  • Agustina D'Urso
  • Seo Hyun Kim
  • Jason H Brickner

National Institute of General Medical Sciences (T32 GM008061)

  • Agustina D'Urso

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

Copyright

© 2022, Sump 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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  1. Bethany Sump
  2. Donna G Brickner
  3. Agustina D'Urso
  4. Seo Hyun Kim
  5. Jason H Brickner
(2022)
Mitotically heritable, RNA polymerase II-independent H3K4 dimethylation stimulates INO1 transcriptional memory
eLife 11:e77646.
https://doi.org/10.7554/eLife.77646

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https://doi.org/10.7554/eLife.77646

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