Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity

  1. Michael P Meers
  2. Telmo Henriques
  3. Christopher A Lavender
  4. Daniel J McKay
  5. Brian D Strahl
  6. Robert J Duronio
  7. Karen Adelman
  8. A Gregory Matera  Is a corresponding author
  1. The University of North Carolina at Chapel Hill, United States
  2. Harvard Medical School, United States
  3. National Institute of Environmental Heatlth Science, United States
  4. Harvard University, United States

Abstract

Histone H3 lysine 36 methylation (H3K36me) is thought to participate in a host of co-transcriptional regulatory events. To study the function of this residue independent from the enzymes that modify it, we used a 'histone replacement' system in Drosophila to generate a non-modifiable H3K36 lysine-to-arginine (H3K36R) mutant. We observed global dysregulation of mRNA levels in H3K36R animals that correlates with the incidence of H3K36me3. Similar to previous studies, we found that mutation of H3K36 also resulted in H4 hyperacetylation. However, neither cryptic transcription initiation, nor alternative pre-mRNA splicing, contributed to the observed changes in expression, in contrast with previously reported roles for H3K36me. Interestingly, knockdown of the RNA surveillance nuclease, Xrn1, and members of the CCR4-Not deadenylase complex, restored mRNA levels for a class of downregulated, H3K36me3-rich genes. We propose a post-transcriptional role for modification of replication-dependent H3K36 in the control of metazoan gene expression.

Data availability

The following data sets were generated
The following previously published data sets were used
    1. Elgin S
    (2013) H3K36me3 abcam L3 Nuc Input expt.2225
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147189).
    1. Elgin S
    (2013) H3K36me3 abcam L3 Nuc Input expt.2226
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147190).
    1. Elgin S
    (2013) H3K36me3 abcam L3 Nuc ChIP expt.2259
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147191).
    1. Elgin S
    (2013) H3K36me3 abcam L3 Nuc ChIP expt.2260
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147192).
    1. Elgin S
    (2013) H3K36me1 L3 Nuc Input expt.2402
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147193).
    1. Elgin S
    (2013) H3K36me1 L3 Nuc Input expt.2404
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147194).
    1. Elgin S
    (2013) H3K36me1 L3 Nuc ChIP expt.2400
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147195).
    1. Elgin S
    (2013) H3K36me1 L3 Nuc ChIP expt.2401
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147196).
    1. Elgin S
    (2013) H3 antibody3 L3 Nuc Input expt.2222
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147289).
    1. Elgin S
    (2013) H3 antibody3 L3 Nuc Input expt.2224
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147290).
    1. Elgin S
    (2013) H3 antibody3 L3 Nuc ChIP expt.2241
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147291).
    1. Elgin S
    (2013) H3 antibody3 L3 Nuc ChIP expt.2242
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147292).
    1. Karpen G
    (2013) H3K36me2 W 14-16 hr OR Emb Input expt.2307
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147547).
    1. Karpen G
    (2013) H3K36me2 W 14-16 hr OR Emb Input expt.2308
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147548).
    1. Karpen G
    (2013) H3K36me2 W 14-16 hr OR Emb ChIP expt.2396
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147549).
    1. Karpen G
    (2013) H3K36me2 W 14-16 hr OR Emb ChIP expt.2397
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147550).
    1. Elgin S
    (2013) H4K16ac(M).L3 Input expt.2402
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200107).
    1. Elgin S
    (2013) H4K16ac(M).L3 Input expt.2404
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200108).
    1. Elgin S
    (2013) H4K16ac(M).L3 ChIP expt.2514
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200109).
    1. Elgin S
    (2013) H4K16ac(M).L3 ChIP expt.2515
    Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200110).

Article and author information

Author details

  1. Michael P Meers

    Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  2. Telmo Henriques

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  3. Christopher A Lavender

    Integrative Bioinformatics Support Group, National Institute of Environmental Heatlth Science, Research Triangle Park, United States
    Competing interests
    No competing interests declared.
  4. Daniel J McKay

    Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  5. Brian D Strahl

    Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  6. Robert J Duronio

    Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  7. Karen Adelman

    Department of Biological Chemistry and Molecular Pharmacology, Harvard University, Boston, United States
    Competing interests
    Karen Adelman, Reviewing editor, eLife.
  8. A Gregory Matera

    Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, United States
    For correspondence
    matera@unc.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6406-0630

Funding

National Institutes of Health (For use of Harvard TRiP lines,R01-GM084947)

  • Michael P Meers
  • A Gregory Matera

National Cancer Institute (Ruth L. Kirschstein Predoctoral Fellowship,F31-CA177088)

  • Michael P Meers

Office of the Director (Epigenomics Roadmap Project,R01-DA036897)

  • Brian D Strahl
  • Robert J Duronio
  • A Gregory Matera

National Institute of Environmental Health Sciences (Intramural Research Program,Z01-ES101987)

  • Karen Adelman

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

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Michael P Meers
  2. Telmo Henriques
  3. Christopher A Lavender
  4. Daniel J McKay
  5. Brian D Strahl
  6. Robert J Duronio
  7. Karen Adelman
  8. A Gregory Matera
(2017)
Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity
eLife 6:e23249.
https://doi.org/10.7554/eLife.23249

Share this article

https://doi.org/10.7554/eLife.23249

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