DNA methylation – the transfer of a methyl group to DNA - is a well-studied epigenetic modification. Although the roles of different DNA methyltransferases have been examined in detail, less is known about the effects of altering methyl group availability. Now, Jacquetta Trasler and co-workers show that paternal deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in methyl group production, leads to loss of sperm DNA methylation in mice and to reproductive decline across generations. The researchers first show that paternal MTHFR deficiency leads to testicular abnormalities, with the testes of the F2 generation being more severely affected than those of the F1 generation. They further report that MTHFR deficiency causes profound genome-wide loss of sperm DNA methylation in both the F1 and F2 generations. Detailed analysis of the hypomethylated regions reveals that they are enriched for evolutionarily young retrotransposons. Moreover, these regions are marked by H3K4me3 and correspond to sites that are subject to late de novo methylation during germline epigenetic reprogramming. These findings lead the authors to propose that the preferential loss of DNA methylation at young retrotransposons, which are normally kept highly methylated during reprogramming, could contribute to the worsened reproductive defect seen in the F2 generation, potentially via increased expression of these retrotransposons. Importantly, these results highlight that epimutations can be passed on to subsequent generations rather than being removed during epigenetic reprogramming.
MTHFR: generating new insights into epigenetic inheritance Free
MTHFR: generating new insights into epigenetic inheritance. Development 1 July 2021; 148 (13): e148_e1303. doi:
Download citation file:
Advertisement
Cited by
The Company of Biologists Workshops

For the last 15 years, our publisher, The Company of Biologists, has provided an apt environment to inspire biology and support biologists through our Workshops series. Read about the evolution of the Workshop series and revisit JEB's experience with hosting the first Global South Workshop.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues

Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 30 May 2025.
Meet our 2025 Pathway to Independence (PI) fellows

We are delighted to announce our third cohort of PI fellows - researchers whom we will be supporting as they transition from postdoc to Principal Investigator. Read about the eight talented fellows chosen, whom we're excited to be working with as they navigate the job market.
In preprints
Did you know that Development publishes perspectives on recent preprints? These articles help our readers navigate the ever-growing preprint literature. Together with our preprint highlights service, preLights, these perspectives help our readers navigate the ever-growing preprint literature. We welcome proposals for ‘In preprints’ articles, so please do get in touch if you’d like to contribute.
the Node: Have your say

Our community site, the Node, is conducting a user survey about the content and the design of the site. Help us shape the Node's future and thank you for being a part of the Node over the last 15 years.