Transient reduction of DNA methylation at the onset of meiosis in male mice
Abstract Background Meiosis is a specialized germ cell cycle that generates haploid gametes. In the initial stage of meiosis, meiotic prophase I (MPI), homologous chromosomes pair and recombine. Extensive changes in chromatin in MPI raise an important question concerning the contribution of epigenet...
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doaj-88cde53dca7447c987a8be8be5eff3f52020-11-24T21:24:20ZengBMCEpigenetics & Chromatin1756-89352018-04-0111111510.1186/s13072-018-0186-0Transient reduction of DNA methylation at the onset of meiosis in male miceValeriya Gaysinskaya0Brendan F. Miller1Chiara De Luca2Godfried W. van der Heijden3Kasper D. Hansen4Alex Bortvin5Department of Embryology, Carnegie Institution for ScienceDepartment of Biology, Johns Hopkins UniversityDepartment of Embryology, Carnegie Institution for ScienceDepartment of Obstetrics and Gynaecology, Erasmus MC, University Medical CenterDepartment of Biostatistics, Johns Hopkins UniversityDepartment of Embryology, Carnegie Institution for ScienceAbstract Background Meiosis is a specialized germ cell cycle that generates haploid gametes. In the initial stage of meiosis, meiotic prophase I (MPI), homologous chromosomes pair and recombine. Extensive changes in chromatin in MPI raise an important question concerning the contribution of epigenetic mechanisms such as DNA methylation to meiosis. Interestingly, previous studies concluded that in male mice, genome-wide DNA methylation patters are set in place prior to meiosis and remain constant subsequently. However, no prior studies examined DNA methylation during MPI in a systematic manner necessitating its further investigation. Results In this study, we used genome-wide bisulfite sequencing to determine DNA methylation of adult mouse spermatocytes at all MPI substages, spermatogonia and haploid sperm. This analysis uncovered transient reduction of DNA methylation (TRDM) of spermatocyte genomes. The genome-wide scope of TRDM, its onset in the meiotic S phase and presence of hemimethylated DNA in MPI are all consistent with a DNA replication-dependent DNA demethylation. Following DNA replication, spermatocytes regain DNA methylation gradually but unevenly, suggesting that key MPI events occur in the context of hemimethylated genome. TRDM also uncovers the prior deficit of DNA methylation of LINE-1 retrotransposons in spermatogonia resulting in their full demethylation during TRDM and likely contributing to the observed mRNA and protein expression of some LINE-1 elements in early MPI. Conclusions Our results suggest that contrary to the prevailing view, chromosomes exhibit dynamic changes in DNA methylation in MPI. We propose that TRDM facilitates meiotic prophase processes and gamete quality control.http://link.springer.com/article/10.1186/s13072-018-0186-0DNA methylationHemimethylationSpermatogenesisLINE-1RetrotransposonMouse |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valeriya Gaysinskaya Brendan F. Miller Chiara De Luca Godfried W. van der Heijden Kasper D. Hansen Alex Bortvin |
spellingShingle |
Valeriya Gaysinskaya Brendan F. Miller Chiara De Luca Godfried W. van der Heijden Kasper D. Hansen Alex Bortvin Transient reduction of DNA methylation at the onset of meiosis in male mice Epigenetics & Chromatin DNA methylation Hemimethylation Spermatogenesis LINE-1 Retrotransposon Mouse |
author_facet |
Valeriya Gaysinskaya Brendan F. Miller Chiara De Luca Godfried W. van der Heijden Kasper D. Hansen Alex Bortvin |
author_sort |
Valeriya Gaysinskaya |
title |
Transient reduction of DNA methylation at the onset of meiosis in male mice |
title_short |
Transient reduction of DNA methylation at the onset of meiosis in male mice |
title_full |
Transient reduction of DNA methylation at the onset of meiosis in male mice |
title_fullStr |
Transient reduction of DNA methylation at the onset of meiosis in male mice |
title_full_unstemmed |
Transient reduction of DNA methylation at the onset of meiosis in male mice |
title_sort |
transient reduction of dna methylation at the onset of meiosis in male mice |
publisher |
BMC |
series |
Epigenetics & Chromatin |
issn |
1756-8935 |
publishDate |
2018-04-01 |
description |
Abstract Background Meiosis is a specialized germ cell cycle that generates haploid gametes. In the initial stage of meiosis, meiotic prophase I (MPI), homologous chromosomes pair and recombine. Extensive changes in chromatin in MPI raise an important question concerning the contribution of epigenetic mechanisms such as DNA methylation to meiosis. Interestingly, previous studies concluded that in male mice, genome-wide DNA methylation patters are set in place prior to meiosis and remain constant subsequently. However, no prior studies examined DNA methylation during MPI in a systematic manner necessitating its further investigation. Results In this study, we used genome-wide bisulfite sequencing to determine DNA methylation of adult mouse spermatocytes at all MPI substages, spermatogonia and haploid sperm. This analysis uncovered transient reduction of DNA methylation (TRDM) of spermatocyte genomes. The genome-wide scope of TRDM, its onset in the meiotic S phase and presence of hemimethylated DNA in MPI are all consistent with a DNA replication-dependent DNA demethylation. Following DNA replication, spermatocytes regain DNA methylation gradually but unevenly, suggesting that key MPI events occur in the context of hemimethylated genome. TRDM also uncovers the prior deficit of DNA methylation of LINE-1 retrotransposons in spermatogonia resulting in their full demethylation during TRDM and likely contributing to the observed mRNA and protein expression of some LINE-1 elements in early MPI. Conclusions Our results suggest that contrary to the prevailing view, chromosomes exhibit dynamic changes in DNA methylation in MPI. We propose that TRDM facilitates meiotic prophase processes and gamete quality control. |
topic |
DNA methylation Hemimethylation Spermatogenesis LINE-1 Retrotransposon Mouse |
url |
http://link.springer.com/article/10.1186/s13072-018-0186-0 |
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