1. Chromosomes and Gene Expression
Download icon

Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis

  1. Christina Ernst
  2. Jeremy Pike
  3. Sarah J Aitken
  4. Hannah K Long
  5. Nils Eling
  6. Lovorka Stojic
  7. Frances Connor
  8. Tim F Rayner
  9. Margus Lukk
  10. Robert J Klose
  11. Claudia Kutter
  12. Duncan T Odom  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Oxford, United Kingdom
  3. Science for Life Laboratory, Sweden
Short Report
  • Cited 3
  • Views 2,210
  • Annotations
Cite this article as: eLife 2016;5:e20235 doi: 10.7554/eLife.20235

Abstract

Most human aneuploidies originate maternally, due in part to the presence of highly stringent checkpoints during male meiosis. Indeed, male sterility is common among aneuploid mice used to study chromosomal abnormalities, and male germline transmission of exogenous DNA has been rarely reported. Here we show that despite aberrant testis architecture, males of the aneuploid Tc1 mouse strain produce viable sperm and transmit human chromosome 21 to create aneuploid offspring. In these offspring, we mapped transcription, transcriptional initiation, enhancer activity, non-methylated DNA and transcription factor binding in adult tissues. Remarkably, when compared with mice derived from female passage of human chromosome 21, the chromatin condensation during spermatogenesis and the extensive epigenetic reprogramming specific to male germline transmission resulted in almost indistinguishable patterns of transcriptional deployment. Our results reveal an unexpected tolerance of aneuploidy during mammalian spermatogenesis, and the surprisingly robust ability of mouse developmental machinery to accurately deploy an exogenous chromosome, regardless of germline transmission.

Data availability

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

Article and author information

Author details

  1. Christina Ernst

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3569-2209
  2. Jeremy Pike

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  3. Sarah J Aitken

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  4. Hannah K Long

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Nils Eling

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  6. Lovorka Stojic

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  7. Frances Connor

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  8. Tim F Rayner

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  9. Margus Lukk

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  10. Robert J Klose

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8726-7888
  11. Claudia Kutter

    Science for Life Laboratory, Stockholm, Sweden
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8047-0058
  12. Duncan T Odom

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    Duncan.Odom@cruk.cam.ac.uk
    Competing interests
    Duncan T Odom, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6201-5599

Funding

Cancer Research UK (A20412)

  • Christina Ernst
  • Sarah J Aitken
  • Nils Eling
  • Frances Connor
  • Tim F Rayner
  • Margus Lukk
  • Claudia Kutter
  • Duncan T Odom

European Research Council (615584)

  • Duncan T Odom

Wellcome (098024/Z/11/Z)

  • Robert J Klose

Wellcome (106563/Z/14/A)

  • Sarah J Aitken

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

Ethics

Animal experimentation: This investigation was approved by the Animal Welfare and Ethics Review Board and followed the Cambridge Institute guidelines for the use of animals in experimental studies under Home Office license PPL 70/7535.

Human subjects: Previously published human data from Ward et al. 2013 were used for comparisons in this study.

Reviewing Editor

  1. Edith Heard, Institut Curie, France

Publication history

  1. Received: August 1, 2016
  2. Accepted: November 14, 2016
  3. Accepted Manuscript published: November 18, 2016 (version 1)
  4. Accepted Manuscript updated: November 22, 2016 (version 2)
  5. Version of Record published: December 16, 2016 (version 3)

Copyright

© 2016, Ernst 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

  • 2,210
    Page views
  • 438
    Downloads
  • 3
    Citations

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

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)

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

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

Further reading

    1. Chromosomes and Gene Expression
    Hiroaki Tachiwana et al.
    Tools and Resources

    In eukaryotes, histone variant distribution within the genome is the key epigenetic feature. To understand how each histone variant is targeted to the genome, we developed a new method, the RhIP (Reconstituted histone complex Incorporation into chromatin of Permeabilized cell) assay, in which epitope-tagged histone complexes are introduced into permeabilized cells and incorporated into their chromatin. Using this method, we found that H3.1 and H3.3 were incorporated into chromatin in replication-dependent and -independent manners, respectively. We further found that the incorporation of histones H2A and H2A.Z mainly occurred at less condensed chromatin (open), suggesting that condensed chromatin (closed) is a barrier for histone incorporation. To overcome this barrier, H2A, but not H2A.Z, uses a replication-coupled deposition mechanism. Our study revealed that the combination of chromatin structure and DNA replication dictates the differential histone deposition to maintain the epigenetic chromatin states.

    1. Chromosomes and Gene Expression
    2. Evolutionary Biology
    Rachel A Johnston et al.
    Research Article Updated

    In some mammals and many social insects, highly cooperative societies are characterized by reproductive division of labor, in which breeders and nonbreeders become behaviorally and morphologically distinct. While differences in behavior and growth between breeders and nonbreeders have been extensively described, little is known of their molecular underpinnings. Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats. By experimentally assigning breeding ‘queen’ status versus nonbreeder status to age-matched littermates, we confirm that queens experience vertebral growth that likely confers advantages to fecundity. However, they also upregulate bone resorption pathways and show reductions in femoral mass, which predicts increased vulnerability to fracture. Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity. However, in mole-rats, concentrated reproduction is also accompanied by costs to bone strength.