Genome-wide maps of chromatin state in folate deficiency mESCs

Folate deficiency causes widespread DNA breakages and is responsible for neural tube defect (NTD). However, little is known about the implications and mechanisms of these DNA instability to NTD. Here, by performing high-throughput sequencing, we generate genome-wide epigenetic profiles and map the distribution of DNA double-strands breaks (DSBs) in folate-antagonist treated embryonic stem cells. We find that DSBs exhibit distinct preference in active promoters and inhibit the interaction between enhancers and promoters. We uncover DSBs affected CTCF binding as a causal link for the abnormal expression of NTD susceptible genes. Finally, we propose a two-ways model for screening NTD susceptible genes and verifying 7 candidate genes in NTD fetuses with low folate level. In summary, our work demonstrate that folate deficiency induced DSBs trigger the dysregulation of NTD susceptible genes through impacting epigenetic regulation. Overall design: Examination of gene expression, chromatin accessibility, 4 histone modifications, CTCF and gH2AX in normal mESC and folate deficiency mESCs.