Loss of KDM5A-mediated H3K4me3 demethylation promotes aberrant neural development by Wnt/β-catenin pathway activation.

ABSTRACT: Neural tube defects (NTDs) are common and severe birth defects. Folate supplementation can prevent NTDs, but the underlying molecular mechanisms are unclear. Aberrant wnt/β-catenin pathway activation leads to defective anteroposterior patterning, resulting in NTDs, but little is known about whether epigenetic factors contribute to this process. Here, we performed ChIP and Cut&Tag to explore H3K4me3 in folate-deficient cells and NTDs mouse models. Our findings show folate deficiency increased H3K4me3 levels at wnt target genes promoters, enhancing their transcription. This effect was mediated by reduced expression of histone demethylase KDM5A, leading to the maintenance of H3K4me3 marks and activation of wnt/β-catenin signalling. Similarly, wnt/β-catenin pathway was activated in KDM5A-KO ce

SUBMITTER: Li J 

PROVIDER: S-EPMC12644828 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature