Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity
- The University of North Carolina at Chapel Hill, United States
- Harvard Medical School, United States
- National Institute of Environmental Heatlth Science, United States
- 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
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Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelityPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE96922).
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H3K36me3 abcam L3 Nuc Input expt.2225Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147189).
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H3K36me3 abcam L3 Nuc Input expt.2226Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147190).
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H3K36me3 abcam L3 Nuc ChIP expt.2259Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147191).
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H3K36me3 abcam L3 Nuc ChIP expt.2260Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147192).
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H3K36me1 L3 Nuc Input expt.2402Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147193).
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H3K36me1 L3 Nuc Input expt.2404Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147194).
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H3K36me1 L3 Nuc ChIP expt.2400Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147195).
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H3K36me1 L3 Nuc ChIP expt.2401Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147196).
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H3 antibody3 L3 Nuc Input expt.2222Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147289).
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H3 antibody3 L3 Nuc Input expt.2224Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147290).
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H3 antibody3 L3 Nuc ChIP expt.2241Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147291).
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H3 antibody3 L3 Nuc ChIP expt.2242Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147292).
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H3K36me2 W 14-16 hr OR Emb Input expt.2307Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147547).
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H3K36me2 W 14-16 hr OR Emb Input expt.2308Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147548).
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H3K36me2 W 14-16 hr OR Emb ChIP expt.2396Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147549).
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H3K36me2 W 14-16 hr OR Emb ChIP expt.2397Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1147550).
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H4K16ac(M).L3 Input expt.2402Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200107).
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H4K16ac(M).L3 Input expt.2404Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200108).
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H4K16ac(M).L3 ChIP expt.2514Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200109).
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H4K16ac(M).L3 ChIP expt.2515Publicly available at the NCBI Gene Expression Omnibus (Accession no: GSM1200110).
Article and author information
Author details
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.
Reviewing Editor
- Elisa Izaurralde, Max Planck Institute for Developmental Biology, Germany
Version history
- Received: November 12, 2016
- Accepted: March 23, 2017
- Accepted Manuscript published: March 27, 2017 (version 1)
- Accepted Manuscript updated: April 7, 2017 (version 2)
- Version of Record published: April 25, 2017 (version 3)
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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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
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