DNA methylation, the charm of dynamics

DNA methylation is one of the key epigenetic markers. It is critical for mammalian development and plays an essential role in diverse biological processes, such as X chromosome inactivation, genomic imprinting and cell-type-specific gene regulation [1]. Previous studies have revealed DNA methylation dynamics in development and disease. It has been postulated that DNA methylation dynamics participate in regulating spatial- and temporal-specific expression of cell identify genes [2]. The identification and characterization of DNA methylation dynamics in cell-type-specific gene regulation remain a subject of great interest [3, 4]. To this end, we present a special issue that assembles a broad spectrum of reviews on DNA methylation dynamics, ranging from basic research in development to translational application in oncology. We have invited some of the most influential researchers in the field of DNA methylation to help us delineate the current state of the art as well as to identify opportunities and challenges for the further development of this exciting field. DNA methylation undergoes great changes from one cell type to another. The detecting of these DNA methylation dynamics relies on methylation maps from different biological status. Advances in sequence- and array-based technologies have helped investigators to profiling the DNA methylomes across multiple tissues and cell lines, which provide us with an opportunity to completely map and dissect the DNA methylation marks on a whole genome or genome-wide scale [5]. Some computational tools have been developed to analyze these large-scale DNA methylomes and detect different kinds of methylation dynamics. In this special issue, Chen et al. [6] discuss various methods in detecting differentially methylated regions, their utility and limitations comprehensively according to data and region types. Liu et al. [7] review the recent state-of-the-art advances in the three levels (genome-wide identification, regulation mechanisms and the function annotation) of the DNA methylation dynamics research, as well as the future perspective of DNA methylation dynamics. More practically, Shicai Fan and Wenming Chi [8] review the computational methods for preprocessing, analyzing and interpreting the cancer methylome data, and highlight biomarker investigation for cancer diagnosis, prognosis and response to treatment. DNA methylation is an essential epigenetic modification for mammalian development and plays important roles in gene regulation during cell development and differentiation. Active DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. Thus, genome-wide DNA methylation analysis in different genomic contexts reveals cell-type-specific DNA methylation patterns that show distinct functional relevance with cell-type specificity. Mining the methylation marks of stem cells, particularly human embryonic stem cells, is valuable for exploring the role of DNA methylation in the maintenance of pluripotency. In this special issue, Suelves et al. [9] summarize published data regarding DNA methylation changes along lineage specification and differentiation programs and propose the importance of DNA methylation dynamics in cellular commitment and differentiation. Although various human cell types may have the same genome, these cells have different methylomes. Yang et al. [10] survey the recent advances on comparative DNA methylation analysis to decipher common and cell-type-specific patterns among multiple cell types. Aberrant methylation can cause multiple diseases, including cancer [11]. There is some controversy about DNA methylation dynamics in cancers, although researchers have done a lot work in cancer analysis. The systematic identification of DNA methylation marks in various cancers and other human diseases is essential for the early diagnosis and targeted therapy. In this special issue, Wang et al. [12] summarize the recent developments of computational methods and software tools in high-throughput methylation data analysis with focus on two aspects: differential methylation analysis and tumor purity estimation in cancer studies. In another review, Veronique G. LeBlanc and Marco A. Marra [13] provide an overview of the current knowledge regarding the role of DNA methylation in adult diffuse gliomas. Han et al. [14] summarize the latest evidence and challenges regarding the role of DNA methylation on hypertension. Xiao et al. [15] survey the crucial roles of DNA methylation in aging and age-related disease and highlight the great potential of DNA methylation as a therapeutic target in preventing age-related diseases and promoting healthy longevity. In-depth studies on DNA methylation abnormalities associated with human disease and aging will be helpful for understanding the mechanisms of carcinogenesis and proposing new treatments for cancer and other diseases. There are also some special focuses in this special issue. The mechanisms behind DNA methylation and demethylation dynamics are discussed by three reviews [7, 9, 10]. Besides methylation dynamic of CpG (5'-C-phosphate-G-3') sites, non-CpG sites also showed cell-type-specific methylation patterns correlated with specific functions in development and cancer [7]. DNA methylation dynamics is one of core regulators in the complex transcriptional regulatory network, which defines cell-type-specific phenotype. The cross talk of DNA methylation and other regulators and other cell-type-specific regulators including transcription factors, histone modifications and enhancers is specially focused by nearly all reviews in this special issue. It should be noted that DNA methylation might play a key role in cell-type identity by regulating ‘super-enhancers’, which have been proposed as large clusters of transcriptional enhancers that promote distinct gene expression profiles for the characterization of cellular phenotypes [7, 9, 10]. Several reviews suggest the mining of methylation markers by integrating large-scale cancer samples for a pan-cancer scale would reveal the different carcinogenesis mechanisms [6, 8, 10, 12, 13]. With regard to mechanism, Ragione et al. [16] reviewed the roles of MeCP2 in the maintenance of chromatin architecture, which appears to be clearly established recently. In conclusion, this special issue weaves together both the past and present of DNA methylation dynamics with a special focus on two important biological processes, development and disease. It has become clear that DNA methylation dynamics can greatly influence cell identity and human health in spatial- and temporal-specific manner. It is our hope that this special issue will stimulate the reader to explore diverse ways to understand the charm of DNA methylation dynamics in development and disease. Many more years of experimental and computational effort are required before we gain a full understanding of the mechanisms behind DNA methylation dynamics, but we are off to a good start. We would like to acknowledge and thank all authors for their valuable contributions. We also thank Dr Alison Bentley from the Briefings Editorial Office for her guidance and support. H.L. was supported, in whole or in part, by the National Natural Science Foundation of China [61403112, 31371334, 81573021 and 61402139] and the Natural Scientific Research Fund of Heilongjiang Provincial [ZD2015003].