INSERM U954 Nutrition, Genetics, and Environmental Risk Exposure, Faculté de Médecine, Nancy Université, Vandoeuvre les Nancy, France.
Mol Nutr Food Res. 2012 Jun;56(6):976-85. doi: 10.1002/mnfr.201100640.
Prenatal folate and methyl donor malnutrition lead to epigenetic alterations that could enhance susceptibility to disease. Methyl-deficient diet (MDD) and fumonisin FB1 are risk factors for neural tube defects and cancers. Evidence indicates that FB1 impairs folate metabolism.
Folate receptors and four heterochromatin markers were investigated in rat fetuses liver derived from dams exposed to MDD and/or FB1 administered at a dose twice higher than the provisional maximum tolerable daily intake (PMTDI = 2 μg/kg/day). Even though folate receptors transcription seemed up-regulated by methyl depletion regardless of FB1 treatment, combined MDD/FB1 exposure might reverse this up-regulation since folate receptors transcripts were lower in the MDD/FB1 versus MDD group. Methyl depletion decreased H4K20me3. Combined MDD/FB1 decreased H4K20me3 even more and increased H3K9me3. The elevated H3K9me3 can be viewed as a defense mechanism inciting the cell to resist heterochromatin disorganization. H3R2me2 and H4K16Ac varied according to this mechanism even though statistical significance was not consistent.
Considering that humans are exposed to FB1 levels above the PMTDI, this study is relevant because it suggests that low doses of FB1 interact with MDD thus contributing to disrupt the epigenetic landscape.
产前叶酸和甲基供体营养不良会导致表观遗传改变，从而增加患病易感性。甲基缺乏饮食（MDD）和伏马菌素 FB1 是神经管缺陷和癌症的危险因素。有证据表明，FB1 会损害叶酸代谢。
研究了暴露于 MDD 和/或 FB1 的母体所产生的胎鼠肝脏中的叶酸受体和四个异染色质标记物，FB1 的给药剂量是暂定最大耐受日摄入量（PMTDI=2μg/kg/天）的两倍。尽管甲基耗竭似乎独立于 FB1 处理而上调了叶酸受体的转录，但 MDD/FB1 联合暴露可能会逆转这种上调，因为 MDD/FB1 组的叶酸受体转录物低于 MDD 组。甲基耗竭降低了 H4K20me3。MDD/FB1 联合降低了 H4K20me3，增加了 H3K9me3。升高的 H3K9me3 可以被视为一种引发细胞抵抗异染色质紊乱的防御机制。H3R2me2 和 H4K16Ac 根据该机制而变化，尽管统计意义不一致。
鉴于人类接触的 FB1 水平高于 PMTDI，因此这项研究具有相关性，因为它表明低剂量的 FB1 与 MDD 相互作用，从而导致表观遗传景观的破坏。
