# Harnessing Nanopore Sequencing to Investigate the Epigenomic Landscape in Molar Incisor Hypomineralization—A Pilot Study

## TL;DR

This pilot study explores DNA methylation differences in a child with molar incisor hypomineralization using nanopore sequencing, suggesting epigenetic factors may contribute to the condition.

## Contribution

The study is the first to investigate the epigenomic landscape of MIH using nanopore sequencing, revealing novel methylation patterns linked to dental development and inflammation.

## Key findings

- 780,141 CpGs showed significantly different methylation levels between MIH and control samples.
- Methylation differences were enriched in genes related to dental morphogenesis and inflammatory processes.
- Distinct methylation of transposable elements and enrichment in ameloblast differentiation and calcium ion binding processes were observed.

## Abstract

Molar incisor hypomineralization (MIH) is a dental condition that affects the enamel of permanent molars and/or incisors, often leading to tooth decay. Although several etiological hypotheses have come forward, including prenatal medical problems and postnatal illness, the pathogenesis of MIH is yet unclear. Aimed at exploring the epigenomic landscape of this dental condition, we collected dental tissue from a MIH-affected child and an age-matched control patient and investigated their DNA methylation status through an in-depth analysis of nanopore long-read sequencing data. We identified 780,141 CpGs with significantly different methylation levels between the samples; intriguingly, the density of these dinucleotides was higher in the regions containing genes involved in dental morphogenesis and inflammatory processes leading to periodontitis. Further examination of 54 genes associated with MIH or hypomineralized second primary molar disorders revealed very distinct methylation of intragenic transposable elements (SINEs, LINEs, and LTRs), while functional profiling analysis of 571 differentially methylated regions genome-wide uncovered significant enrichment processes including ameloblasts differentiation and calcium ion binding, as well as SP1 and other zinc finger transcription factors. Taken together, our findings suggest that DNA methylation could play a role in the pathogenesis of MIH and represent a stepping stone towards a comprehensive understanding of this multifactorial disorder.