TY - JOUR
T1 - Cross-Talk between miRNAs from the Dlk1-Dio3 Locus and Histone Methylation to Protect Male Cerebellum from Methyl Donor Deficiency
AU - Willekens, Jeremy
AU - Mosca, Pauline
AU - Burt-Oberecken, Nathan
AU - Laugeais, Edgar
AU - Kaoma, Tony
AU - Bernardin, François
AU - Vallar, Laurent
AU - Dimofski, Pauline
AU - Renaud, Mathilde
AU - Lambert, Laetitia
AU - Leheup, Bruno
AU - Guéant, Jean Louis
AU - Leininger-Muller, Brigitte
AU - Dreumont, Natacha
N1 - Funding Information:
The original elements used in the graphical abstract and in Figure 3A have partially been created with BioRender.com ( https://biorender.com/ , accessed on 19 January 2023). The authors would like to thank the ORION program for its contribution to the funding of NBO's research internship. This work has benefited from a government grant managed by the Agence Nationale de la Recherche with the reference ANR‐20‐SFRI‐0009. A grant from Région Lorraine supported this work.
Publisher Copyright:
© 2022 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH© 2023 Wiley-VCH GmbH.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - epigenetics
KW - folate
KW - histone
KW - microRNA
KW - rat cerebellum
UR - http://www.scopus.com/inward/record.url?scp=85169903384&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/37672803
U2 - 10.1002/mnfr.202300040
DO - 10.1002/mnfr.202300040
M3 - Article
C2 - 37672803
SN - 1613-4125
VL - 67
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 21
M1 - e2300040
ER -