Analysis of the Epigenetic Signature of Cell Reprogramming by Computational DNA Methylation Profiles

Abstract

Background: DNA methylation plays an important role in the reprogramming process. Understanding the underlying molecular mechanism of reprogramming is crucial for answering fundamental questions regarding the transition of cell identity. Methods: In this study, based on the genome-wide DNA methylation data from different cell lines, comparative methylation profiles were proposed to identify the epigenetic signature of cell reprogramming. Results: The density profile of CpG methylation showed that pluripotent cells are more polarized than Human Dermal Fibroblasts (HDF) cells. The heterogeneity of iPS has a greater deviation in the DNA hypermethylation pattern. The result of regional distribution showed that the differential CpG sites between pluripotent cells and HDFs tend to accumulate in the gene body and CpG shelf regions, whereas the internal differential methylation CpG sites (DMCs) of three types of pluripotent cells tend to accumulate in the TSS1500 region. Furthermore, a series of endogenous markers of cell reprogramming were identified based on the integrative analysis, including focal adhesion, pluripotency maintenance and transcription regulation. The calcium signaling pathway was detected as one of the signatures between NT cells and iPS cells. Finally, the regional bias of DNA methylation for key pluripotency factors was discussed. Our studies provide new insight into the barrier identification of cell reprogramming. Conclusion: Our studies analyzed some epigenetic markers and barriers of nuclear reprogramming, hoping to provide new insight into understanding the underlying molecular mechanism of reprogramming.