Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis

Misty Good, Tianjiao Chu, Patricia Shaw, Lora McClain, Austin Chamberlain, Carlos Castro, Jamie M. Rimer, Belgacem Mihi, Qingqing Gong, Lila S. Nolan, Krista Cooksey, Laura Linneman, Pranjal Agrawal, David N. Finegold, David Peters

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation. Methods: Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data. Results: We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation. Conclusions: We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.[Figure not available: see fulltext.].

Original languageEnglish
Article number190
JournalClinical Epigenetics
Volume12
Issue number1
DOIs
StatePublished - Dec 2020

Keywords

  • DNA methylation
  • Epigenetics
  • Intestinal epithelium
  • Necrotizing enterocolitis
  • Neonatal

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