{"doi":"10.1002/mnfr.202000769","title":"Low Maternal Dietary Intake of Choline Regulates Toll‐Like Receptor 4 Expression Via Histone H3K27me3 in Fetal Mouse Neural Progenitor Cells","abstract":"<jats:sec><jats:title>Scope</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>Timed‐pregnant <jats:italic>Nestin‐CFPnuc</jats:italic> 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 <jats:italic>Tlr4</jats:italic> transcription, causing premature neuronal differentiation and enhanced ethanol‐induced NLRP3 inflammasome activation. No changes in DNA methylation at the <jats:italic>Tlr4</jats:italic> 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 <jats:italic>Tlr4</jats:italic> expression. Conversely, the application of catalytically inactive Cas9 with EZH2 to increase H3K27me3 at the <jats:italic>Tlr4</jats:italic> promoter causes reduced <jats:italic>Tlr4</jats:italic> expression.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These data reveal an epigenetic mechanism for the effect of maternal choline availability on brain development, suggesting a likely intervention for neurodevelopmental diseases.</jats:p></jats:sec>","journal":"Molecular Nutrition &amp; Food Research","year":2021,"id":622516,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1608489,"name":"Xuedan Chen","orcid":null,"position":1,"is_corresponding":false},{"id":1608490,"name":"Limeng Dai","orcid":null,"position":2,"is_corresponding":false},{"id":1608491,"name":"Jiming Ma","orcid":null,"position":3,"is_corresponding":false},{"id":16277,"name":"Qiming Zhang","orcid":"0000-0003-4282-2996","position":4,"is_corresponding":false},{"id":669337,"name":"Song Qu","orcid":"0000-0003-2134-0226","position":5,"is_corresponding":false},{"id":649645,"name":"Yun Bai","orcid":"0000-0002-2688-9229","position":6,"is_corresponding":false},{"id":638787,"name":"Yanyan Wang","orcid":"0000-0001-5482-2585","position":7,"is_corresponding":false},{"id":1608488,"name":"Xingying Guan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Low Maternal Dietary Intake of Choline Regulates Toll‐Like Receptor 4 Expression Via Histone H3K27me3 in Fetal Mouse Neural Progenitor Cells","abstract":"<jats:sec><jats:title>Scope</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>Timed‐pregnant <jats:italic>Nestin‐CFPnuc</jats:italic> 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 <jats:italic>Tlr4</jats:italic> transcription, causing premature neuronal differentiation and enhanced ethanol‐induced NLRP3 inflammasome activation. No changes in DNA methylation at the <jats:italic>Tlr4</jats:italic> 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 <jats:italic>Tlr4</jats:italic> expression. Conversely, the application of catalytically inactive Cas9 with EZH2 to increase H3K27me3 at the <jats:italic>Tlr4</jats:italic> promoter causes reduced <jats:italic>Tlr4</jats:italic> expression.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These data reveal an epigenetic mechanism for the effect of maternal choline availability on brain development, suggesting a likely intervention for neurodevelopmental diseases.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33274576","pmcid":null,"openalex_id":"https://openalex.org/W33274576","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81573153","title":null},{"funder_name":"Army Medical University","grant_id":"2019XBK31","title":null},{"funder_name":"Chongqing Science and Technology Commission","grant_id":"cstc2018jcyjAX0499","title":null}],"total_grants":3,"fwci":0.0,"citation_percentile":0.0028849,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/mnfr.202000769","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mnfr.202000769","host_type":"publisher"},{"url":"https://dialnet.unirioja.es/servlet/articulo?codigo=663917","host_type":"repository"}],"fields_of_study":["Insect and Arachnid Ecology and Behavior"],"mesh_terms":["Animals","Mice, Transgenic","Choline Deficiency","Choline","Ethanol","Lysine","Histones","Cell Differentiation","Epigenesis, Genetic","Gene Expression Regulation, Developmental","Pregnancy","Female","Toll-Like Receptor 4","Maternal Nutritional Physiological Phenomena","Neurogenesis","Inflammasomes","Neural Stem Cells","NLR Family, Pyrin Domain-Containing 3 Protein"],"keywords":["Humanities","Art","Choline","Toll-like receptor 4","histone modification","Inflammasome","Neural Progenitor Cell"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T19:55:38.005553Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}