Cross-Talk between miRNAs from the Dlk1-Dio3 Locus and Histone Methylation to Protect Male Cerebellum from Methyl Donor Deficiency

Jeremy Willekens, Pauline Mosca, Nathan Burt-Oberecken, Edgar Laugeais, Tony Kaoma, François Bernardin, Laurent Vallar, Pauline Dimofski, Mathilde Renaud, Laetitia Lambert, Bruno Leheup, Jean Louis Guéant, Brigitte Leininger-Muller, Natacha Dreumont*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review


Scope: Disruption of the one carbon metabolism during development, i.e., following a gestational vitamin B9 and B12 deficiencies, is involved in birth defects and brain development delay. Using a rat nutritional model, consisting of pups born to dams fed a vitamin B9 and B12 deficient diet (MDD), the study previously reports molecular and cellular alterations in the brain, in a sex dependent manner, with females being more affected than males. The study hypothesizes that epigenetic modifications could participate in the sex differences is observed. Methods and results: The study investigates lysine methylation of histones and expression of microRNAs in the cerebellum of MDD male and female pups. The study reports a differential regulation of H3K36Me2 and H4K20Me3 between males and females, in response to MDD. Moreover, distinct regulation of Kmt5b and Kdm2a expression by miR-134-5p and miR-369-5p from the Dlk1-Dio3 locus, contributes to the maintenance of expression of genes involved in synaptic plasticity. Conclusion: These results could explain the neuroprotection to MDD that male pups display. The work will contribute to the understanding of the consequences of vitamin starvation on brain development, as well as how the epigenome is affected by one carbon metabolism disruption.

Original languageEnglish
Article numbere2300040
JournalMolecular Nutrition and Food Research
Early online date6 Sept 2023
Publication statusE-pub ahead of print - 6 Sept 2023


  • epigenetics
  • folate
  • histone
  • microRNA
  • rat cerebellum


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