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.
Chip-Seq analysis of human chromosome 21 after its passage through either the female or male mouse germlinePublicly available at the EBI European Nucleotide Archive (accession no: E-MTAB-4913).
BioCAP-Seq analysis of human chromosome 21 after its passage through either the mouse male germlinePublicly available at the EBI European Nucleotide Archive (accession no: E-MTAB-4930).
RNA-Seq in liver of Tc1 mice carrying human chromosome 21 passaged through either the female or male germlinePublicly available at the EBI European Nucleotide Archive (accession no: E-MTAB-4912).
E-MTAB-1104 - ChIP-seq of human and transgenic mouse adult liver, testes & kidney tissue to investigate epigenetic comparisonPublicly available at the EBI European Nucleotide Archive (accession no: E-MTAB-1104).
E-MTAB-2633 - ChIP-Seq analysis of regulatory evolution in 20 mammalsPublicly available at the EBI European Nucleotide Archive (accession no: E-MTAB-2633).
E-TABM-722 - ChIP-seq of Canis familiaris, Gallus gallus, Mus musculus, Homo sapiens, Monodelphis domestica to investigate CEBPA and HNF4a binding in five vertebratesPublicly available at the EBI European Nucleotide Archive (accession no: E-TABM-722).
An evolutionarily conserved DNA-encoded logic shapes CpG island formationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE72208).
- Christina Ernst
- Sarah J Aitken
- Nils Eling
- Frances Connor
- Tim F Rayner
- Margus Lukk
- Claudia Kutter
- Duncan T Odom
- Duncan T Odom
- Robert J Klose
- Sarah J Aitken
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Edith Heard, Institut Curie, France
© 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.
Mosquitoes transmit numerous pathogens, but large gaps remain in our understanding of their physiology. To facilitate explorations of mosquito biology, we have created Aegypti-Atlas (http://aegyptiatlas.buchonlab.com/), an online resource hosting RNAseq profiles of Ae. aegypti body parts (head, thorax, abdomen, gut, Malpighian tubules, ovaries), gut regions (crop, proventriculus, anterior and posterior midgut, hindgut), and a gut time course of blood meal digestion. Using Aegypti-Atlas, we provide insights into regionalization of gut function, blood feeding response, and immune defenses. We find that the anterior and posterior midgut possess digestive specializations which are preserved in the blood-fed state. Blood feeding initiates the sequential induction and repression/depletion of multiple cohorts of peptidases. With respect to defense, immune signaling components, but not recognition or effector molecules, show enrichment in ovaries. Basal expression of antimicrobial peptides is dominated by holotricin and gambicin, which are expressed in carcass and digestive tissues, respectively, in a mutually exclusive manner. In the midgut, gambicin and other effectors are almost exclusively expressed in the anterior regions, while the posterior midgut exhibits hallmarks of immune tolerance. Finally, in a cross-species comparison between Ae. aegypti and Anopheles gambiae midguts, we observe that regional digestive and immune specializations are conserved, indicating that our dataset may be broadly relevant to multiple mosquito species. We demonstrate that the expression of orthologous genes is highly correlated, with the exception of a ‘species signature’ comprising a few highly/disparately expressed genes. With this work, we show the potential of Aegypti-Atlas to unlock a more complete understanding of mosquito biology.
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.