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

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

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...

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Published in:Molecular nutrition & food research Vol. 67; no. 21; p. e2300040
Main Authors: Willekens, Jeremy, Mosca, Pauline, Burt‐Oberecken, Nathan, Laugeais, Edgar, Kaoma, Tony, Bernardin, François, Vallar, Laurent, Dimofski, Pauline, Renaud, Mathilde, Lambert, Laetitia, Leheup, Bruno, Guéant, Jean‐Louis, Leininger‐Muller, Brigitte, Dreumont, Natacha
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc 01-11-2023
Wiley-VCH Verlag
Subjects:
Birth defects
Brain
Carbon
Cerebellum
Congenital defects
Disruption
Epigenetics
Females
Gender differences
Gene expression
Histones
Juveniles
Life Sciences
Lysine
Males
Metabolism
Methylation
MicroRNAs
miRNA
Neuroprotection
Nutrient deficiency
Preadipocyte factor 1
Sex differences
Synaptic plasticity
microRNA
folate
histone
epigenetics folate histone microRNA rat cerebellum
rat cerebellum
epigenetics
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Summary: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.
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ISSN:1613-4125
1613-4133
DOI:10.1002/mnfr.202300040