LAUSR

The high-order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi-omics data on the large variety of samples, and hopefully a common picture of carcinogenesis. In particular, we are interested in the question of whether an underlying origin DNA sequence exists for these epigenetic alterations. The human genome consists of two types of megabase-sized domain based on the distribution of CpG islands (CGIs) that show distinct structural, epigenetic and transcriptional properties: CGI-rich and CGI-poor domains. Through an integrated analysis of chromatin structure, DNA methylation and RNA-sequencing data, we found that, in carcinogenesis, the two different types of domain display different structural changes, and have an increased number of DNA-methylation differences and transcriptional-level differences, compared with in non-cancer cells. We also compared the structural features among carcinogenesis, senescence and mitosis, showing the possible connection between chromatin structure and cell state, which could affect vital cancer-related properties. In summary, chromatin structure, DNA methylation and gene expression, as well as their changes observed in several types of cancers, show a dependence on multi-scale DNA sequence heterogeneity.