Low Maternal Dietary Intake of Choline Regulates Toll‐Like Receptor 4 Expression Via Histone H3K27me3 in Fetal Mouse Neural Progenitor Cells. Issue 2 (13th December 2020)

• Record Type: Journal Article
• Authors: Guan, Xingying; Chen, Xuedan; Dai, Limeng; Ma, Jiming; Zhang, Qiming; Qu, Song; Bai, Yun; Wang, Yanyan
• Is Part Of: Molecular nutrition & food research. Volume 65:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-13
• Subjects: choline -- histone modification -- inflammasome -- neural progenitor cell -- toll‐like receptor 4; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202000769
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Choline is an essential nutrient and a primary dietary source of methyl groups that are vital for brain development. Low choline (LC) in the maternal diet during pregnancy alters neurogenesis in the fetal brain and leads to low cognitive performance. However, the key signaling pathways that are sensitive to maternal choline supply during neural progenitor cell (NPC) development and the epigenetic mechanisms by which choline availability regulates gene expression are unclear. Methods and results: Timed‐pregnant Nestin‐CFPnuc transgenic mice are fed either a control diet or LC diet during E11–17. Gene expression changes in sorted E17 NPCs are identified by RNA sequencing. A maternal LC diet significantly increases Tlr4 transcription, causing premature neuronal differentiation and enhanced ethanol‐induced NLRP3 inflammasome activation. No changes in DNA methylation at the Tlr4 gene promoter region are detected; however, a 70% decrease in H3K27me3 is observed in the LC‐treated NPCs. Inhibition of EZH2 decreases H3K27me3 levels and increases Tlr4 expression. Conversely, the application of catalytically inactive Cas9 with EZH2 to increase H3K27me3 at the Tlr4 promoter causes reduced Tlr4 expression. Conclusion: These data reveal an epigenetic mechanism for the effect of maternal choline availability on brain development, suggesting a likely intervention for neurodevelopmental diseases. Abstract : Choline is important for brain development. It is found that low maternal dietary intake of choline increases Toll‐like receptor 4 (TLR4) transcription in neural progenitor cells, which results in premature neuronal differentiation and exacerbated ethanol‐induced inflammasome activation. This effect is caused by a decrease in H3K27me3 at the Tlr4 promoter.These findings elucidate the relationship between choline availability and brain development.