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With the advent of next-generation sequencing technology, genome-wide maps of DNA methylation are now available. The Thoroughbred horse is bred for racing, while the Jeju horse is a traditional Korean horse bred for racing or food. The methylation profiles of equine organs may provide genomic clues underlying their athletic traits. We have developed a database to elucidate genome-wide DNA methylation patterns of the cerebrum, lung, heart, and skeletal muscle from Thoroughbred and Jeju horses. Using MeDIP-Seq, our database provides information regarding significantly enriched methylated regions beyond a threshold, methylation density of a specific region, and differentially methylated regions (DMRs) for tissues from two equine breeds. It provided methylation patterns at 784 gene regions in the equine genome. This database can potentially help researchers identify DMRs in the tissues of these horse species and investigate the differences between the Thoroughbred and Jeju horse breeds.

Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethylated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.

Mobile genetic elements within genomes have been known to drive genome evolution in diverse ways. Since developing high-technology for whole-genome sequencing, many researchers have focused on not only how mobile genetic elements have affected the evolution of genes and their function, particularly of human and mammals, but also how these elements involve in gene activation or inactivation associated with a number of human diseases. Here we describe what kind of biological changes by mobile genetic elements contribute to disease, especially cancer and present an overview of what is known about this large, and largely unexplored, segment of the genome. Finally, we discuss understanding the genomic changes or cellular responses to genotoxic stress such as radiation may permit to implicate for potential clinical application.

DNA methylation is an essential biochemical modification that regulates gene expression. Exercise induces changes in gene expression that adapt as metabolic changes in the blood. We provide a database for the epigenetic changes after horse exercise ( http://www.primate.or.kr/hexdb ). Horse Exercise Epigenetic Database (HExDB) explicates the change in genome-wide DNA methylation patterns after exercise. Exercise changes the genome-wide epigenetic patterns, and understanding the regions that change is important for confirming exercise physiological mechanisms. For this purpose, our database provides information on differentially methylated regions after exercise that pass a set threshold. A total of 784 genes based on NCBI RefSeq were identified as differentially methylated in equines after exercise. Our database provides clues for the study of exercise-related epigenetic pathways in the thoroughbred horse.

Mounting evidence suggests that inflammatory bowel disease (IBD) is caused by genetic predisposition of various genes as well as an abnormal interaction with environmental factors, resulting in epigenetic alterations. It has become evident that epigenetic factors play a significant contributory role during disease development. Additionally, DNA methylation has been reported to be correlated with the development of IBD. In the present study, we examined the role of DNA hypermethylation in Crohn's disease (CD) patients. The transcription elongation regulator 1-like (TCERG1L) gene, which has been previously reported to be highly frequently methylated in colon tumors was selected as a candidate for the early detection of biomarkers for colon cancer patients. DNA methylation of TCERG1L in 101 serum samples of CD patients was examined. Results of conventional MSP analysis revealed high methylation [57% (58/101)] of serum samples in CD patients. The DNA methylation pattern of TCEEG1L was confirmed using bisulfate sequencing analysis. The results of the present study suggest that using regular colonoscopic surveillance sensitive DNA methylation markers may detect serum samples of CD patients, leading to reduced risk or prevention of the progression of advanced stages of disease.

Transposable elements (TEs) are repetitive sequences dispersed throughout mammalian genomes, and they occupy important genetic positions. TEs have been shown to have both harmful and beneficial effects such as exonization, polyadenylation, and/or altering transcription rates in various vertebrate genomes. However, to the best of our knowledge, no study has yet considered the relationship between TEs and horse genes. In this study, we examined the contribution of TEs to the horse genome by collecting TEs inserted within mRNA genes. By screening the abundance, distribution, and orientation of TEs, we found that the majority of TE insertions belong to retroelements and DNA elements, most of which exist in the coding sequences of horse genes. In addition, the MIR, L1, L2, ERVL, and ERVL-MaLR subfamilies were found to be the most abundant in both non-LTR and LTR elements. Retroelements (LTRs, LINEs, and SINEs) among the TEs inserted in the coding sequences showed a preference for antisense orientation. The most pronounced imbalance in insertional orientation was observed in LINEs, which represent 40 % of all TEs in antisense orientation. Through these analyses, we identified that a total of 1310 TEs have been integrated into horse mRNA genes and small fractions of them have been exonized into coding sequences.

Eukaryotic genomes comprise numerous retroelements that have a major impact on the structure and regulation of gene function. Retroelements are regulated by epigenetic controls, and they generate multiple miRNAs that are involved in the induction and progression of genomic instability. Elucidation of the biological roles of retroelements deserves continuous investigation to better understand their evolutionary features and implications for disease.

Cartilage increases flexibility of motion and helps protect the body from physical shock. Strong physical shock or some biological factor could cause joint disease. ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) has been related to degradation of aggrecans in cartilage. It has been associated with joint disease, which could influence the ability of horses to exercise. Here, we performed sequence analysis and expression profiling of the ADAMTS4 gene in thoroughbred horses. Quantitative real-time RT-PCR data indicated that higher expression of the ADAMTS4 gene appeared in the cartilage tissues compared to those of pancreas, stomach, lung and colon. The expression pattern was also higher in the muscle tissues after exercise than before exercise. These data could be of great use for further studies in relation to both horse racing and joint disease.

Retroelements play important roles in primate evolution. Specifically, human endogenous retroviruses (HERVs) and Alu elements are primate-specific retroelements. In addition, SVA elements belong to the youngest family of hominid non-long terminal repeat (LTR) retrotransposons. Retroelements can affect adjacent gene expression, supplying cis-regulatory elements, splice sites, and poly-A signals. We developed a database, GEnome-wide Browser for RETroelement (GEBRET, http://neobio.cs.pusan.ac.kr/~gebre/), for comparing the distribution of primate-specific retroelements and adjacent genes. GEBRET database components include 47,381 HERVs, 53,924 Alus and 4639 SVAs in five primate genomes of human, chimpanzee, orangutan, rhesus macaque, and marmoset. Host genes located upstream of a retroelement were also visualized and classified as five categories (0.0, 0.5, 1.0, 2.0, and 3.0Kb). Our results suggest that retroelements preferentially integrate into the distal promoter region relative to the core promoter region. GEBRET database is designed to investigate the distribution of retroelements (HERVs, Alus and SVAs) in the primate genomes that have been sequenced. Our software will be useful in the field to study the impact of retroelements on primate genome evolution.

Genetic mutations by gene fusion result from chromosomal rearrangement, trans-splicing, and intergenic splicing. Trans-splicing is a phenomenon in which two pre-mRNAs grow together into one. We analyzed the trans-splicing products in embryonic stem cells. By using bioinformatic tools, 70 trans-splicing transcripts were identified. They are classified into 6 types according to fusion pattern: 5'UTR-5'UTR, 5'UTR-3'UTR, 3'UTR-3'UTR, 5'UTR-CDS, 3'UTR-CDS, CDS-CDS. The fusion products are more abundant in CDS regions than in UTR regions, which contain multiple intron numbers. Chromosome analysis showing gene fusion via trans-splicing indicated that chromosomes 17 and 19 were activated. These data are of great use for further studies in relation to fusion genes and human diseases.

Recent studies have reported that embryonic stem (ES) cell-associated gene expression signatures have been identified in poorly differentiated tumors, revealing a link between ES cell identity and cancer cells. Cancer cells originate from cancer stem cells (CSCs). Both types of cells share common properties such as self-renewal and heterogeneity. CSCs are also resistant to conventional chemotherapy and radiotherapy. Here, we show similar gene expression patterns between ES cells and ionizing radiation (IR)-treated cancer cells. Using genome-wide transcriptome analysis, we compared the gene expression profiles among ES cells, cancer cells, and irradiated cancer cells, and identified a subset of similar gene expression patterns between ES cells and irradiated cancer cells, indicated by hierarchical clustering. These gene expression patterns were then confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses. Using bioinformatic analyses, these candidate genes are also associated with various biological pathways related to stemness in cancer. Taken together, our data suggest that identification of common molecular characteristics between ES cells and irradiated cancer cells is important to understand the properties of cancer stem cells and their resistance to radiotherapy.

Background Exposure to ionizing radiation (IR) results in the simultaneous activation or downregulation of multiple signaling pathways that play critical roles in cell type-specific control of survival or death. IR is a well-known genotoxic agent and human carcinogen that induces cellular damage through direct and indirect mechanisms. However, its impact on epigenetic mechanisms has not been elucidated, and more specifically, little information is available regarding genome-wide DNA methylation changes in cancer cells after IR exposure. Recently, genome-wide DNA methylation profiling technology using the Illumina HumanMethylation450K platform has emerged that allows us to query >450,000 loci within the genome. This improved technology is capable of identifying genome-wide DNA methylation changes in CpG islands and other CpG island-associated regions. Results In this study, we employed this technology to test the hypothesis that exposure to IR not only induces differential DNA methylation patterns at a genome-wide level, but also results in locus- and gene-specific DNA methylation changes. We screened for differential DNA methylation changes in colorectal cancer cells after IR exposure with 2 and 5 Gy. Twenty-nine genes showed radiation-induced hypomethylation in colon cancer cells, and of those, seven genes showed a corresponding increase in gene expression by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, we performed chromatin immunoprecipitation (ChIP) to confirm that the DNA-methyltransferase 1 (DNMT1) level associated with the promoter regions of these genes correlated with their methylation level and gene expression changes. Finally, we used a gene ontology (GO) database to show that a handful of hypomethylated genes induced by IR are associated with a variety of biological pathways related to cancer. Conclusion We identified alterations in global DNA methylation patterns and hypomethylation at specific cancer-related genes following IR exposure, which suggests that radiation exposure plays a critical role in conferring epigenetic alterations in cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1229-6) contains supplementary material, which is available to authorized users.

Background DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known. Results We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density. Conclusions We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.

The horse BMAL1 gene encodes the brain and muscle Arnt-like protein 1, which is a key regulator of circadian rhythmic systems in most organs and cells. The first exon of the horse-specific BMAL1 gene is produced by an exonization event of LINE3 (CR1) and SINE (MIR) was detected by bioinformatic analysis. Alternative variants generated by cassette exon event in various horse tissues were also detected by RT-PCR amplification and sequencing. The cDNA sequences of the horse transcripts (BMAL1a, BMAL1b) contain additional 21 bp and 71 bp fragments relative to horse BMAL1. Quantitative real-time RT-PCR was performed to compare the expression patterns between transcript variants in various horse tissues. The results of these experiments showed splice variants that were widely expressed in most tissues. Furthermore, they were highly expressed in cerebellum, heart, and kidney.

In the mitochondrial matrix, the OXCT1 gene catalyzes the reversible transfer of coenzyme A from succinyl-CoA to acetoacetate in a reaction related to energy production from ketone bodies. Here, horse OXCT1 gene containing coenzyme A transferase domain was identified in the transcriptome analysis of cDNAs derived from skeletal muscles. Horse OXCT1 gene consisted of 1761 [corrected] nucleotide sequences with an open reading frame of 1560 nucleotides encoding a protein of 520 putative amino acid residues.The number of non-synonymous substitutions was lower than the number of synonymous substitutions in the OXCT1 genes of other species, indicating that purifying selection occurred in the OXCT1 genes during evolutionary radiation. Quantitative real-time RT-RCR analysis showed a dominant expression pattern of horse OXCT1 gene in the cerebrum, heart, and skeletal muscle. Different expression levels of horse OXCT1 transcripts between before- and after-exercise samples were also measured in the skeletal muscles of six horses. These data could be of great use for further investigation of the relationship between energy products and horse OXCT1 gene.

Muscle glycogen Phosphorylase (PYGM) has been shown to catalyze the degradation of glycogen to glucose-1-phosphate. The PYGM gene can contribute to providing energy to the body by disassembling the glycogen in muscle. Here, we analyzed the genomic structure and expression of the PYGM gene in the thoroughbred horse. The PYGM gene, containing several transposable elements (MIRs, LINEs, and MERs), was highly conserved in mammalian genomes. In order to understand the expression of the horse PYGM gene, we performed quantitative RT-PCR using 11 thoroughbred horse tissue samples. The horse PYGM gene was broadly expressed in all tissues tested. In particular, the highest expression of the horse PYGM gene was observed in skeletal muscle tissue relative to the other tissues. Interestingly, the horse PYGM gene contains fewer mobile elements than its human ortholog, resulting in an increase in the structural stability of the PYGM gene sequence. This study provides insights into the genomic structure of the horse PYGM gene that may be useful in future studies of its association with exercise capability.