1,721,030 research outputs found
DNA methylation: an epigenetic mark of cellular memory
No full textGenome-wide association studies (GWAS) have remarkably advanced insight into the genetic basis of schizophrenia (SCZ). Still, most of the functional variance in disease risk remains unexplained. Hence, there is a growing need to map genetic variability-to-genes-to-functions for understanding the pathophysiology of SCZ and the development of better treatments. Genetic variation can regulate various cellular functions including DNA methylation, an epigenetic mark with important roles in transcription and the mediation of environmental influences. Methylation quantitative trait loci (meQTLs) are derived by mapping levels of DNA methylation in genetically different, genotyped individuals and define loci at which DNA methylation is influenced by genetic variation. Recent evidence points to an abundance of meQTLs in brain tissues whose functional contributions to development and mental diseases are still poorly understood. Interestingly, fetal meQTLs reside in regulatory domains affecting methylome reconfiguration during early brain development and are enriched in loci identified by GWAS for SCZ. Moreover, fetal meQTLs are preserved in the adult brain and could trace early epigenomic deregulation during vulnerable periods. Overall, these findings highlight the role of fetal meQTLs in the genetic risk for and in the possible neurodevelopmental origin of SCZ.
DNA methylation: a cause and consequence of type 2 diabetes
No full textDNA methylation is a relatively stable epigenetic modification that can regulate and stabilize gene expression patterns and hence establish cell identity. Because metabolic intermediates are key factors of DNA methylation and demethylation, perturbations in metabolic homeostasis can trigger alterations in cell-specific patterns of DNA methylation and contribute to disease development, including type 2 diabetes (T2D). During the past decade, genome-wide DNA methylation studies of T2D have expanded our knowledge of the molecular mechanisms underlying T2D. This review summarizes case-control studies of the DNA methylome of T2D and discusses DNA methylation as both a cause and consequence of T2D. Therefore, DNA methylation has potential as a promising T2D biomarker that can be applied to the development of therapeutic strategies for T2D.
Genomic and epigenomic heterogeneity in molecular subtypes of gastric cancer
No full textGastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr viruspositive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.open
Dorsal and Ventral Hippocampus Differentiate in Functional Pathways and Differentially Associate with Neurological Disease-Related Genes during Postnatal Development
No full textThe dorsal and ventral regions of the hippocampus are important in cognitive and emotional processing, respectively. Various approaches have revealed the differential molecular and structural characteristics, and functional roles of the hippocampus. Recent RNA sequencing (RNA-seq) technology has enriched our understanding of the hippocampus by elucidating more detailed information on gene expression patterns. However, no RNA-seq？based study on gene profiles in the developing hippocampus has been reported. Using RNA-seq？based bioinformatic analysis in conjunction with quantitative real-time polymerase chain reaction analysis and a comparison of in situhybridization data obtained from the Allen Brain Atlas, we provide a thorough analysis of differentially expressed genes in the dorsal and ventral hippocampus at specific developmental ages representing the postnatally maturing hippocampus. Genes associated with particular functional pathways and marker genes for particular neurological diseases were found to be distinctively segregated within either the dorsal or ventral hippocampus at specific or at all developmental ages examined. We also report novel molecular markers enriched in the dorsal or ventral hippocampus. Taken together, this study provides insights into the molecular mechanisms underlying physiological functions linked to the dorsal or ventral hippocampus. The information provided in the study also contributes to a better understanding of brain functions and serves as a resource for future studies on the pathophysiology of dorsal and ventral hippocampal functions
Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes
No full textSLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR-218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.open
Cell-free miR-27a, a potential diagnostic and prognostic biomarker for gastric cancer
No full textMicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate the usefulness of miRNAs for gastric cancer detection. We initially examined plasma miRNA expression levels in a screening cohort consisting of 15 patients with gastric cancer and 15 healthy controls from Korean population, using TaqMan quantitative real-time polymerase chain reaction. We observed that the expression level of miR-27a was significantly higher in patients with gastric cancer than in healthy controls, whereas the miR-21 and miR-155a expression levels were not significantly higher in the patients with gastric cancer. Therefore, we further validated the miR-27a expression level in 73 paired gastric cancer tissues and in a validation plasma cohort from 35 patients with gastric cancer and 35 healthy controls. In both the gastric cancer tissues and the validation plasma cohort, the miR-27a expression levels were significantly higher in patients with gastric cancer. Receiver-operator characteristic (ROC) analysis of the validation cohort, revealed an area under the ROC curve value of 0.70 with 75% sensitivity and 56% specificity in discriminating gastric cancer. Thus, the miR-27a expression level in plasma could be a useful biomarker for the diagnosis and/or prognosis of gastric cancer.open
H2B monoubiquitylation is a 5'-enriched active transcription mark and correlates with exon-intron structure in human cells
No full textH2B monoubiquitylation (H2Bub1), which is required for multiple methylations of both H3K4 and H3K79, has been implicated in gene expression in numerous organisms ranging from yeast to human. However, the molecular crosstalk between H2Bub1 and other modifications, especially the methylations of H3K4 and H3K79, remains unclear in vertebrates. To better understand the functional role of H2Bub1, we measured genome-wide histone modification patterns in human cells. Our results suggest that H2Bub1 has dual roles, one that is H3 methylation dependent, and another that is H3 methylation independent. First, H2Bub1 is a 5′-enriched active transcription mark and co-occupies with H3K79 methylations in actively transcribed regions. Second, this study shows for the first time that H2Bub1 plays a histone H3 methylationsindependent role in chromatin architecture. Furthermore, the results of this work indicate that H2Bub1 is largely positioned at the exon-intron boundaries of highly expressed exons, and it demonstrates increased occupancy in skipped exons compared with flanking exons in the human and mouse genomes. Our findings collectively suggest that a potentiating mechanism links H2Bub1 to both H3K79 methylations in actively transcribed regions and the exon-intron structure of highly expressed exons via the regulation of nucleosome dynamics during transcription elongation.open
Cyclin Y-mediated transcript profiling reveals several important functional pathways regulated by Cyclin Y in hippocampal neurons.
No full textCyclin Y (CCNY), which is a cyclin protein known to play a role in cell division, is unexpectedly and thus interestingly expressed in non-proliferating neuronal cells. There have been only a few studies reporting the neuronal functions of CCNY in synapse remodeling and hippocampal long-term potentiation. Therefore, we here provide global and comprehensive information on the putative functions of CCNY in biological and functional pathways in neuronal systems. We adopted high-throughput RNA-sequencing technology for analyzing transcriptomes regulated by CCNY and utilized bioinformatics for identifying putative molecules, biological processes, and functional pathways that are possibly connected to CCNY functions in hippocampal neuronal cells of rats. We revealed that several enriched annotation terms and pathways associated with CCNY expression within neurons, including apoptosis, learning or memory, synaptic plasticity, actin cytoskeleton, focal adhesion, extracellular matrix-receptor interaction and chemokine signaling pathway are targeted by CCNY. In addition, the mRNA levels of some genes enriched for those annotation terms and pathways or genes reported to be altered in Alzheimer's disease mouse model were further validated by quantitative real-time PCR in hippocampal neuronal cells. The present study provides an excellent resource for future investigations of CCNY functions in neuronal systems
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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