The Molecular Mechanism of KDM5A in the Development of Neural Tube Defects Caused by Folate Deficiency
Neural tube defects(NTDs)represent a critical area of study within congenital anomalies,with folate known for its preventative role.However,the mechanisms underlying its protective effects re-main largely unknown.This study investigates the potential molecular mechanisms involving lysine dem-ethylase 5A(KDM5A)and its subsequent alteration of histone H3K4me3 in the development of NTDs under folate deficiency.We used chromatin immunoprecipitation along with Cut&Tag to examine the function of KDM5A in a low-folate cell model and a mouse model of folate-deficient NTDs.Quantitative reverse transcription PCR(qRT-PCR)and Western blot analyses demonstrated a marked reduction in KDM5A expression in the low-folate cell model(P＜0.05).In addition,chromatin immunoprecipitation(ChIP)followed by quantitative PCR(ChIP-qPCR)analysis confirmed the increased accumulation of histone H3K4me3 in the promoter regions of important neurodevelopmental genes,Axin2 and Atoh1,with folate deficiency(P＜0.05).By creating a KDM5A-knockout cell model,Cut&Tag experiments was used to confirm the preferential enrichment of H3K4me3 on neurodevelopmental genes.In the brains of folate-deficient NTDs models,decreased expression of KDM5A and upregulated Axin2 and Atoh1 expression were observed,along with increased H3K4me3 enrichment at respective gene promoters(P＜0.05).Col-lectively,these findings highlight the important function of KDM5A in NTDs with folate deficiency.KDM5A affects the expression of genes related to neurodevelopment by modifying H3K4me3 downstream.This study enhances our comprehension of the development of NTDs by examining the impact of disrupted folate metabolism and abnormal regulation of histone modification by KDM5A.It provides valuable in-sights into potential treatments for reducing birth defects and improving reproductive health.
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