Charting Genomic Regions Implicated in Transgenerational Epigenetic Inheritance

DNA methylation plays a vital role in gene regulation and transcription and these epigenetic modifications were shown to be influenced by exterior factors like the environment. However, methylation patterns are erased at two major reprogramming/demethylation waves which prevents their transmission to the next generation. The focus of this study is to examine regions that retain methylation through both reprogramming waves and are therefore potential candidates for transgenerational epigenetic inheritance. To test these putative regions, publicly available whole genome bisulfite sequence datasets were analyzed using Bismark. The data was divided into genomic bins and filtered using varying stringency levels. Bins from each filtration step were annotated using Annotatr package in R. In addition, tests for association and enrichment were carried using various tools including ChromHMM for chromatin structure analysis, TEtranscripts for transposable elements enrichment and Great analysis for predictions of cis regulatory elements. Annotation results indicated that regions escaping methylation reprogramming are enriched for CpG islands and 5’ UTRs. ChromHMM analysis revealed high significance for repetitive elements following the most stringent filtering criteria. Further investigation of transposable elements led to the identification of a high enrichment for Alu and L1 families, which are known for their dynamic methylation patterns during epigenetic reprogramming. Lastly, Great analysis indicated significance for mTOR signaling pathway.