Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/20235 |
| _version_ | 1811227403662393344 |
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| author | Christina Ernst Jeremy Pike Sarah J Aitken Hannah K Long Nils Eling Lovorka Stojic Michelle C Ward Frances Connor Timothy F Rayner Margus Lukk Robert J Klose Claudia Kutter Duncan T Odom |
| author_facet | Christina Ernst Jeremy Pike Sarah J Aitken Hannah K Long Nils Eling Lovorka Stojic Michelle C Ward Frances Connor Timothy F Rayner Margus Lukk Robert J Klose Claudia Kutter Duncan T Odom |
| author_sort | Christina Ernst |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:41:55Z |
| format | Article |
| id | doaj.art-1f142675989441129d0e1c5ce8d2c48e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:41:55Z |
| publishDate | 2016-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1f142675989441129d0e1c5ce8d2c48e2022-12-22T03:38:03ZengeLife Sciences Publications LtdeLife2050-084X2016-11-01510.7554/eLife.20235Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosisChristina Ernst0https://orcid.org/0000-0002-3569-2209Jeremy Pike1Sarah J Aitken2Hannah K Long3Nils Eling4Lovorka Stojic5Michelle C Ward6Frances Connor7Timothy F Rayner8Margus Lukk9Robert J Klose10https://orcid.org/0000-0002-8726-7888Claudia Kutter11https://orcid.org/0000-0002-8047-0058Duncan T Odom12https://orcid.org/0000-0001-6201-5599Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom; Department of Histopathology, Addenbrooke’s Hospital, Cambridge, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United states; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United StatesCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute, Stockholm, SwedenCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United KingdomMost 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.https://elifesciences.org/articles/20235meiosismale germlineepigenetic reprogramminganeuploidy |
| spellingShingle | Christina Ernst Jeremy Pike Sarah J Aitken Hannah K Long Nils Eling Lovorka Stojic Michelle C Ward Frances Connor Timothy F Rayner Margus Lukk Robert J Klose Claudia Kutter Duncan T Odom Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis eLife meiosis male germline epigenetic reprogramming aneuploidy |
| title | Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis |
| title_full | Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis |
| title_fullStr | Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis |
| title_full_unstemmed | Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis |
| title_short | Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis |
| title_sort | successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis |
| topic | meiosis male germline epigenetic reprogramming aneuploidy |
| url | https://elifesciences.org/articles/20235 |
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