DNA Methylome Mapping Identifies Epigenetic Abnormalities in Intestinal Lymphocyte Regulation in Human Necrotizing...

Area of Science:

• Gastroenterology
• Epigenetics
• Immunology

Background:

• Necrotizing enterocolitis (NEC) pathogenesis involves environmental factors and epigenetic changes in animal models.
• The DNA methylation signature in human NEC patients remains unexamined.

Purpose of the Study:

• To characterize the DNA methylation signature and its functional implications in the human intestine affected by NEC.

Main Methods:

• Compared DNA methyltransferases (DNMTs) in NEC versus control intestinal tissue.
• Analyzed genome-wide DNA methylation using reduced representation bisulfite sequencing (RRBS).
• Confirmed gene methylation and expression via bisulfite genomic sequencing (BGS) and RT-qPCR.

Main Results:

• Reduced DNMT3A expression (mRNA and protein) observed in NEC.
• Global hypomethylation detected in NEC lesions, except for CpG islands.
• Identified 287 differentially methylated regions (DMRs) in NEC, with 123 promoter CGI-located.
• Four lymphocyte-regulating genes (ZNF335, MPL, RASAL3, KDM6A) were hypermethylated and downregulated in NEC.

Conclusions:

• Established a novel link between epigenetic alterations and lymphocyte regulation in human NEC.
• Findings suggest potential diagnostic and therapeutic relevance of these epigenetic changes for NEC.