Background: Paternally expressed gene 10 (PEG10) is believed to be a key imprinted gene involved in placenta formation. However, its role in human folate-related spina bifida (SB) remains unclear.
Methods: The methylation status of the germline differentially methylated region (gDMR) in the PEG10/sarcoglycan epsilon (SGCE) imprinted cluster was compared between SB patients and control samples. Moreover, the influence of ectopic PEG10 expression on apoptosis was assessed to explore the underlying mechanisms related to folate deficiency-induced aberrant gDMR methylation in SB.
Results: The case group exhibited a significant increase in the methylation level of the gDMR and a marked reduction in the mRNA and protein expression of PEG10 compared with the control group. A prominent negative correlation was found between the folate level in brain tissue and gDMR methylation status (r = -0.62, P = 0.001). A cell model treated with a demethylating agent showed a significant elevation of PEG10 transcription level, as well as other imprinted genes in this cluster. In addition, the inhibition of PEG10 was found to be accompanied by aberrant activation of apoptosis in SB.
Conclusions: Our findings suggest that disturbed gDMR methylation of the PEG10/SGCE cluster due to folate deficiency is involved in SB through aberrant activation of apoptosis.
Impact: Disturbed genomic imprinting has been verified to be involved in neural tube defects (NTDs). However, little is known about the effect of ectopic expression of imprinted gene PEG10 on human NTDs. Aberrant methylation status of the germline differentially methylated region (gDMR) of PEG10/SGCE cluster due to folate deficiency has been found to result in the inhibition of PEG10 and has a marked association with an increased occurrence of spina bifida. Inhibited expression of PEG10 partly is found to be related to the abnormal activation of apoptosis in spina bifida.
© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.