Advance epigenetics methods in biomedicine

As the field of epigenetics is rapidly expanding, interest in exploration of novel technologies to decode the epigenetic landmarks that are related to biomedical science has dramatically increased. These finely designed tools and strategies that enable to detect, quantify, and image the chromatin state greatly advance epigenetics field and support important breakthroughs in this area. The advancement of epigenetics methodologies utilizes multiple strategies through, for example, high-quality antibodies, chromatin functional assays, imaging tools, high-throughput sequencing technologies and integrated bioinformatics pipelines to reveal chromatin states at multiple dimensions. The goal of this special issue is to introduce the advance technologies in the field of epigenetics that have been applied to investigate epigenetic mechanisms related to biomedical studies. This issue will help the readers to understand the basis of epigenetics and advanced technologies in the field, and provide essential instructions to assist the researchers to choose the suitable methods in their epigenetics studies. Ten papers are included in this special issue to discuss diverse aspects of epigenetics techniques that focus on decoding different epigenetic mechanisms including DNA methylation, histone modifications, non-coding RNAs.

DNA methylation is the most important epigenetic mechanism that has been intensively investigated. In mammalian cells, the major DNA methylation modification pattern is 5-methylcytosine (5mC), which is involved in adding a methyl group to the 5-position of the cytosine ring in CpG dinucleotides. Until today many conventional techniques are widely used to analyze DNA methylation contents. Pajares et al. describe the most commonly used methods including bisulfite conversion-based methods, restriction enzyme-based approaches, and affinity enrichment-based assays to evaluate specific DNA methylation status, which provide the theoretical basis and the framework of common techniques for DNA methylation detection [1]. Specifically, Morselli et al. present a Targeted Bisulfite Sequencing method that can be applied to biomarker discovery [2]. This method combines the relatively low cost of methylation arrays and digital signals of bisulfite sequencing that allows one to assess the status of a fraction of the CpG sites in the genome of an organism. Detecting and mapping technologies for studying genome-wide DNA methylation status has gained rapid development. Li et al. discuss different DNA methylation analysis technologies involved in detection of global DNA methylation profiling [3].

Histone modification is another important epigenetic regulation that can affect gene transcriptional activities through dynamically altering chromatin structure. Most of the technologies that have been developed to study functions and dynamics of histone modifications are based on the platform of chromatin immunoprecipitation (ChIP) assay. Nakato et al. present a practical workflow for genome-wide analysis of histone modifications via various advanced ChIP-sequencing (ChIP-seq) applications including conventional ChIP-seq and single-cell ChIP-seq analysis [4]. In particular, Wang and his colleagues propose a mini review discussing a method that is used to identify centromeric DNAs through ChIP-seq in plants [5]. The assembly of centromeric regions has become one of the most intractable tasks in whole-genome sequencing due to the enrichment of highly repetitive DNA sequences in most eukaryotic centromeres. This mini review provides knowledgeable insights for high-quality evaluation of centromere assembly via centromere ChIP-seq mapping.

Non-coding RNAs (ncRNAs) have been implicated as important epigenetic codes that actively participate in multiple physiological and pathological processes. Research on ncRNAs has exponentially advanced and many technologies have been developed to identify novel transcripts and better understand the diverse roles of ncRNAs in gene regulation. Zhou et al. present a systemic computational screening to predict tRNA-derived fragments (tRFs)-target gene interactions (TGIs) through Argonaute proteins-mediated crosslinking-immunoprecipitation followed by high-throughput sequencing (CLIP-seq) [6]. Dumbović et al. describe protocols to analyze three-dimensional data of spatial positioning of RNA- and protein-containing domains in individual cells using a combination of STimulated Emission Depletion (STED) super resolution microscopy, single molecule RNA (smRNA) FISH and immunofluorescence [7]. These protocols can be employed for single-cell imaging of complex nuclear RNA-protein interactions. CRISPR-dCas9 can function as an epigenetic editing tool and CRISPR-dCas9-epigenetic effectors (EE) complexes could be exploited to alter cancerous epigenetic features associated with different cancer hall-marks. Rahman and Tollefsbol discuss the rationale of epigenetic editing with CRISPR-dCas9 as a therapeutic strategy against cancer, and review ongoing improvements of short guide RNAs (sgRNA)-dCas9 methodology in the field [8].

The expanding epigenetics area leads to a surge in high-throughput sequencing technologies, which require systematic bioinformatic and biostatistic tools/pipelines for processing of large volumes of datasets and identifying useful information in this “omic” era. In this perspective, Arora et al. present different computational methods and next-generation sequencing approaches ranging from library preparation, different sequencing platforms and analytical techniques to decode epigenomic profiling including DNA methylation and histone modifications [9].

Finally, the Guest Editor of this special issue, Dr. Yuanyuan Li presents a comprehensive review and summarizes the most contemporary methods as well as novel technologies in the field of epigenetics [10]. This special issue will be useful to provide the reader with a set of contemporary and advanced technologies in the rapidly developing field of epigenetics.