Methylome

Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpanzees, which have a 1.2% DNA sequence divergence, of sperm, the frontal cortices, B cells, and neutrophils. We revealed that species-specific differentially methylated regions (S-DMRs), ranging from several hundred bp to several kb, were frequently associated with sequence changes in transcription factor binding sites and insertions of Alu and SVA retrotransposons...

The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle...

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions...

Single-cell mRNA sequencing, which permits whole transcriptional profiling of individual cells, has been widely applied to study growth and development of tissues and tumors. Resolving cell cycle for such groups of cells is significant, but may not be adequately achieved by commonly used approaches. Here we develop a traveling salesman problem and hidden Markov model-based computational method named reCAT, to recover cell cycle along time for unsynchronized single-cell transcriptome data. We independently test reCAT for accuracy and reliability using several data sets...

This review provides updates on the efforts for the development of prognostic and predictive markers in colorectal cancer based on the race/ethnicity of patients. Since the clinical consequences of genetic and molecular alterations differ with patient race and ethnicity, the usefulness of these molecular alterations as biomarkers needs to be evaluated in different racial/ethnic groups. To accomplish personalized patient care, a combined analysis of multiple molecular alterations in DNA, RNA, microRNAs (miRNAs), metabolites, and proteins in a single test is required to assess disease status in a precise way...

An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin...

Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16∆E7...

Enhancer is critical cis regulatory elements in gene expression. To understand whether and how the aberrant enhancer activation may contribute to cancer risk, the differentially methylated enhancers (eDMRs) in normal and malignant breast tissues were identified and analyzed. By incorporating genome-wide chromatin interaction, integrated analysis of eDMRs and target gene expression identified 1,272 enhancer-promoter pairs. Surprisingly, two functionally distinct groups of genes were identified in these pairs, one showing better correlation to enhancer methylation (eRGs) and the other showing better correlation to promoter methylation (pRGs), and the former group is functionally enriched with cancer related genes...

BACKGROUND: Studies of epigenetics and transcriptional activity in adolescents may provide knowledge about possible preventive strategies of depression. METHODS: We present a methylome-wide association study (MWAS) and cohort validation analysis of depression in adolescents, in two separate cohorts: discovery (n=93) and validation data set 1 (n=78). The genome-wide methylation pattern was measured from whole blood using the Illumina 450K array. A second validation cohort, validation data set 2, consists of post-mortem brain biopsies from depressed adults (n=58)...

DNA methylation is altered in many types of disease, including metastatic colorectal cancer. However, the methylome has not yet been fully described in archival formalin-fixed paraffin embedded (FFPE) samples in the context of matched fresh-frozen (FF) tumor material at base-pair resolution using a targeted approach. Using next-generation sequencing, we investigated three pairs of matched FFPE and FF samples to determine the extent of their similarity. We identified a 'bowing' pattern specific to FFPE samples categorized by a lower CG proportion at the start of sequence reads...

AIMS: Archived newborn bloodspots are valuable sample collections for genetic and epigenetic disease research. However, they have often been stored for long periods of time, under less than ideal circumstances, and nucleic acid yields can be low, particularly when samples become limiting. We wished to determine whether the quantity and quality of genomic DNA (gDNA) isolated from a single, surgical bloodspot punch (2 mm dia.) were adequate for accurate and reliable DNA methylome profiling on the Illumina HumanMethylation450 array...

Motivation: Microarrays are widely used to quantify DNA methylation because they are economical, require only small quantities of input DNA and focus on well-characterized regions of the genome. However, pre-processing of methylation microarray data is challenging because of confounding factors that include background fluorescence, dye bias and the impact of germline polymorphisms. Therefore, we present valuable insights and a framework for those seeking the most optimal pre-processing method through a data-driven approach...

Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4-13 years), using data drawn from the Avon Longitudinal Study of Parents and Children...

DNA methylation is a critical epigenetic regulator of development in mammals and social insects, but its significance in development outside these groups is not understood. Here we investigated the genome-wide dynamics of DNA methylation in a mollusc model, the oyster Crassostrea gigas, from the egg to the completion of organogenesis. Large-scale methylation maps reveal that the oyster genome displays a succession of methylated and non methylated regions, which persist throughout development. Differentially methylated regions (DMRs) are strongly regulated during cleavage and metamorphosis...

Sexual differentiation has long been considered "epigenetic," although the meaning of that word has shifted over time. Here we track the evolution of ideas about epigenetics in sexual differentiation, and identify principles that have emerged from recent studies. Experiments manipulating a particular epigenetic mechanism during neonatal life demonstrate a role for both histone acetylation and DNA methylation in the development of sex differences in the brain and behavior of rodents. In addition, hormone-dependent sex differences in the number of neurons of a particular phenotype may be programmed by differences in DNA methylation early in life...

Using the latest sequencing and optical mapping technologies, we have produced a high-quality de novo assembly of the apple (Malus domestica Borkh.) genome. Repeat sequences, which represented over half of the assembly, provided an unprecedented opportunity to investigate the uncharacterized regions of a tree genome; we identified a new hyper-repetitive retrotransposon sequence that was over-represented in heterochromatic regions and estimated that a major burst of different transposable elements (TEs) occurred 21 million years ago...

BACKGROUND: Methylation of CG dinucleotides constitutes a critical system of epigenetic memory in bony vertebrates, where it modulates gene expression and suppresses transposon activity. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing. This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates...

BACKGROUND: Cutaneous melanoma is the deadliest skin cancer, with an increasing incidence and mortality rate. Currently, staging of patients with primary melanoma is performed using histological biomarkers such as tumor thickness and ulceration. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, we aimed to identify novel biomarkers providing additional clinical information over current factors using unbiased genome-wide DNA methylation analyses...

STUDY QUESTION: Does ICSI induce specific DNA methylation changes in the resulting offspring? SUMMARY ANSWER: Although several thousand analyzed CpG sites (throughout the genome) displayed significant between-group methylation differences, both ICSI and spontaneously conceived children varied within the normal range of methylation variation. WHAT IS KNOWN ALREADY: Children conceived by ART have increased risks for medical problems at birth and to the extent of present knowledge also in later life (i...

DNA methylation is known to play an important role in various developmental processes in plants. However, there is a general lack of understanding about the possible functions of DNA methylation in fruit trees. Using callus as a model, methylome, transcriptome and metabolite changes were assessed after treatment with the DNA methyltransferase inhibitor 5-azacytidine (5azaC). Genome-wide methylome analysis revealed the demethylation of a diverse of genes, including many genes encoding transcription factors (TFs), genes involved in biological processes, and the up-regulation of a wide range of transposable elements (TEs)...