SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity

Abstract

C. elegans SET-9 and SET-26 are highly homologous paralogs that share redundant functions in germline development, but SET-26 alone plays a key role in longevity and heat stress response. SET-26 is broadly expressed, but SET-9 is only detectable in the germline, which likely account for their different biological roles. SET-9 and SET-26 bind to H3K4me3 with adjacent acetylation marks in vitroand in vivo. In the soma, SET-26 acts through DAF-16 to modulate longevity. In the germline, SET-9 and SET-26 restrict H3K4me3 domains around SET-9 and SET-26 binding sites, and regulate the expression of specific target genes, with critical consequence on germline development. SET-9 and SET-26 are highly conserved and our findings provide new insights into the critical role of these H3K4me3 readers in germline function and longevity.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE108848 and GSE100623.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Wenke Wang

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Amaresh Chaturbedi

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Minghui Wang

    Computational Biology Service Unit, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Serim An

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Satheeja Santhi

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Siu Sylvia Lee

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    For correspondence
    sylvia.lee@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9767-0056

Funding

National Institutes of Health (R01 grant AG024425)

  • Siu Sylvia Lee

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

Reviewing Editor

  1. Sean P Curran, University of Southern California, United States

Version history

  1. Received: January 10, 2018
  2. Accepted: April 30, 2018
  3. Accepted Manuscript published: May 1, 2018 (version 1)
  4. Version of Record published: June 20, 2018 (version 2)

Copyright

© 2018, Wang 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

  • 4,050
    Page views
  • 476
    Downloads
  • 17
    Citations

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

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. Wenke Wang
  2. Amaresh Chaturbedi
  3. Minghui Wang
  4. Serim An
  5. Satheeja Santhi
  6. Siu Sylvia Lee
(2018)
SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity
eLife 7:e34970.
https://doi.org/10.7554/eLife.34970

Share this article

https://doi.org/10.7554/eLife.34970

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Monica Salinas-Pena, Elena Rebollo, Albert Jordan
    Research Article

    Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of ribosomal DNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-Seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.

    1. Chromosomes and Gene Expression
    Signe Penner-Goeke, Elisabeth B Binder
    Insight

    A technique called mSTARR-seq sheds light on how DNA methylation may shape responses to external stimuli by altering the activity of sequences that control gene expression.