Similar Datasets
Project description:Whole genome-bisulfite sequencing has revealed that methylomes differ dramatically in a cell type-specific manner. However, the global mechanisms of maintenance of DNA methylation patterns and their functional consequences are not clear. Using a combination of novel haplotype-resolved methylomes and publicly available data, we show that three distinct classes of methylomes that differ by the proportion of partially and highly methylated domains are characteristic of stem and progenitor, somatic and transformed cells. We provide evidence that three mechanisms can account for most of the differences between these three classes of methylomes. The first, protection of promoters and cis-acting regulatory elements from DNA methylation by DNA-binding proteins, keeps regulatory elements unmethylated. The second, DNA replication-associated maintenance of DNA methylation, is highly efficient in stem cells, moderately efficient in somatic cells, and very inefficient in transformed cells, and sets variable basal levels of methylation characteristic of the partially methylated domains of each cell type. The third, transcriptional elongation-associated gene-body DNA methylation is responsible for the formation of highly methylated domains in somatic and transformed cells. We show that partitioning of the genome into partially and highly methylated domains is associated with different mechanisms of gene silencing.
2019-07-23 | GSE84998 | GEO
Project description:Whole genome-bisulfite sequencing has revealed that methylomes differ dramatically in a cell type-specific manner. However, the global mechanisms of maintenance of DNA methylation patterns and their functional consequences are not clear. Using a combination of novel haplotype-resolved methylomes and publicly available data, we show that three distinct classes of methylomes that differ by the proportion of partially and highly methylated domains are characteristic of stem and progenitor, somatic and transformed cells. We provide evidence that three mechanisms can account for most of the differences between these three classes of methylomes. The first, protection of promoters and cis-acting regulatory elements from DNA methylation by DNA-binding proteins, keeps regulatory elements unmethylated. The second, DNA replication-associated maintenance of DNA methylation, is highly efficient in stem cells, moderately efficient in somatic cells, and very inefficient in transformed cells, and sets variable basal levels of methylation characteristic of the partially methylated domains of each cell type. The third, transcriptional elongation-associated gene-body DNA methylation is responsible for the formation of highly methylated domains in somatic and transformed cells. We show that partitioning of the genome into partially and highly methylated domains is associated with different mechanisms of gene silencing.
2019-07-23 | GSE84999 | GEO
Project description:Evidence That Three Classes of Methylomes Specific for Stem, Somatic and Transformed Cells Are Set by Three Independent Mechanisms
| PRJNA335850 | ENA
Project description:To evaluate the role of fluid and Na+ balance in the development of exercise-associated hyponatremia (EAH), changes in serum Na+ concentrations ([Na+]) and in body weight were analyzed in 2,135 athletes in endurance events. Eighty-nine percent of athletes completed these events either euhydrated (39%) or with weight loss (50%) and with normal (80%) or elevated (13%) serum [Na+]. Of 231 (11%) athletes who gained weight during exercise, 70% were normonatremic or hypernatremic, 19% had a serum [Na+] between 129-135 mmol/liter, and 11% a serum [Na+] of <129 mmol/liter. Serum [Na+] after racing was a linear function with a negative slope of the body weight change during exercise. The final serum [Na+] in a subset of 18 subjects was predicted from the amount of Na+ that remained osmotically inactive at the completion of the trial. Weight gain consequent to excessive fluid consumption was the principal cause of a reduced serum [Na+] after exercise, yet most (70%) subjects who gained weight maintained or increased serum [Na+], requiring the addition of significant amounts of Na+ (>500 mmol) into an expanded volume of total body water. This Na+ likely originated from osmotically inactive, exchangeable stores. Thus, EAH occurs in athletes who (i) drink to excess during exercise, (ii) retain excess fluid because of inadequate suppression of antidiuretic hormone secretion, and (iii) osmotically inactivate circulating Na+ or fail to mobilize osmotically inactive sodium from internal stores. EAH can be prevented by insuring that athletes do not drink to excess during exercise, which has been known since 1985.
| S-EPMC1311740 | biostudies-literature
Project description:We describe psychophysical performance of two stroke patients with lesions in distinct cortical regions in the left hemisphere. Both patients were selectively impaired on direction discrimination in several local and global second-order but not first-order motion tasks. However, only patient FD was impaired on a specific bi-stable motion task where the direction of motion is biased by object similarity. We suggest that this bi-stable motion task may be mediated by a high-level attention or position based mechanism indicating a separate neurological substrate for a high-level attention or position-based mechanism. Therefore, these results provide evidence for the existence of at least three motion mechanisms in the human visual system: a low-level first- and second-order motion mechanism and a high-level attention or position-based mechanism.
| S-EPMC3422620 | biostudies-literature
Project description:The structural relationships among human alkaline phosphatase isoenzymes from placenta, bone, kidney, liver and intestine were investigated by using three criteria. 1. Immunochemical characterization by using monospecific antisera prepared against either the placental isoenzyme or the liver isoenzyme distinguishes two antigenic groups: bone, kidney and liver isoenzymes cross-react with anti-(liver isoenzyme) serum, and the intestinal and placental isoenzymes cross-react with the anti-(placental isoenzyme) antiserum. 2. High-resolution two-dimensional electrophoresis of the 32P-labelled denatured subunits of each enzyme distinguishes three groups of alkaline phosphatase: (a) the liver, bone and kidney isoenzymes, each with a unique isoelectric point in the native form, can be converted into a single form by treatment with neuraminidase; (b) the placental isoenzyme, whose position also shifts after removal of sialic acid; and (c) the intestinal isoenzyme, which is distinct from all other phosphatases and is unaffected by neuraminidase digestion. 3. Finally, we compare the primary structure of each enzyme by partial proteolytic-peptide 'mapping' in dodecyl sulphate/polyacrylamide gels. These results confirm the primary structural identity of liver and kidney isoenzymes and the non-identity of the placental and intestinal forms. These data provide direct experimental support for the existence of at least three alkaline phosphatase genes.
| S-EPMC1161126 | biostudies-other
Project description:A cheap, open source 3D printer (Creality Ender 3) is transformed into an Open Hardware, programmable syringe pump set. Only 3 parts need to be purchased outside of the printer kit. All other parts are either in the Ender 3 kit, or can be 3D printed. No prior knowledge in electronics or programming languages is required. The pumps are controlled by the 3D printer firmware and motherboard and programmed in simple G-code text files. The total cost of a three pumps setup is ∼€170. The pumps are capable of reaching stable flows down to 5 µL/min using cheap, disposable 10 mL syringes. Higher flow speeds are also achievable, in the order of mL/min.
| S-EPMC9123459 | biostudies-literature
Project description:Retinoid dysregulation may be an important factor in the etiology of schizophrenia. This hypothesis is supported by three independent lines of evidence that triangulate on retinoid involvement in schizophrenia: (i) congenital anomalies similar to those caused by retinoid dysfunction are found in schizophrenics and their relatives; (ii) those loci that have been suggestively linked to schizophrenia are also the loci of the genes of the retinoid cascade (convergent loci); and (iii) the transcriptional activation of the dopamine D2 receptor and numerous schizophrenia candidate genes is regulated by retinoic acid. These findings suggest a close causal relationship between retinoids and the underlying pathophysiological defects in schizophrenia. This leads to specific strategies for linkage analyses in schizophrenia. In view of the heterodimeric nature of the retinoid nuclear receptor transcription factors, e.g., retinoid X receptor beta at chromosome 6p21.3 and retinoic acid receptor beta at 3p24.3, two-locus linkage models incorporating genes of the retinoid cascade and their heterodimeric partners, e.g., peroxisome proliferator-activated receptor alpha at chromosome 22q12-q13 or nuclear-related receptor 1 at chromosome 2q22-q23, are proposed. New treatment modalities using retinoid analogs to alter the downstream expression of the dopamine receptors and other genes that are targets of retinoid regulation, and that are thought to be involved in schizophrenia, are suggested.
| S-EPMC33865 | biostudies-literature
Project description:Examination of closely related species pairs is suggested for evolutionary comparisons of different degrees of polyphagy, which we did here with three taxa of lepidopteran herbivores, Spodoptera spp (S. littoralis, S. frugiperda maize (C) and rice (R) strains) for a RNAseq analysis of the midguts from the 3rd instar insect larvae for differential metabolic responses after feeding on pinto bean based artificial diet vs maize leaves. Paired-end (2×100 bp) Illumina HiSeq2500 sequencing resulted in a total of 24, 23, 24, and 21 million reads for the SF-C-Maize, SF-C-Pinto, SF-R-Maize, SF-R Pinto, and a total of 35 and 36 million reads for the SL-Maize and SL-Pinto samples, respectively. After quality control measures, a total of 62.2 million reads from SL and 71.7 million reads from SF were used for transcriptome assembly (TA). The resulting final de novo reference TA (backbone) for the SF taxa contained 37,985 contigs with a N50 contig size of 1030 bp and a maximum contig length of 17,093 bp, while for SL, 28,329 contigs were generated with a N50 contig size of 1980 bp and a maximum contig length of 18,267 bp. The data presented herein contains supporting information related to our research article Roy et al. (2016) http://dx.doi.org/10.1016/j.ibmb.2016.02.006[1].
| S-EPMC4910185 | biostudies-literature
Project description:Methylomic analyses typically require substantial amounts of DNA, thus hindering studies involving scarce samples. Here, we show that microfluidic diffusion-based reduced representative bisulfite sequencing (MID-RRBS) permits high-quality methylomic profiling with nanogram-to-single-cell quantities of starting DNA. We used the microfluidic device, which allows for efficient bisulfite conversion with high DNA recovery, to analyse genome-wide DNA methylation in cell nuclei isolated from mouse brains and sorted into NeuN+ (primarily neuronal) and NeuN- (primarily glial) fractions, and to establish cell-type-specific methylomes. Genome-wide methylation and methylation in low-CpG-density promoter regions showed distinct patterns for NeuN+ and NeuN- fractions from the mouse cerebellum. The identification of substantial variations in the methylomic landscapes of the NeuN+ fraction of the frontal cortex of mice chronically treated with an atypical antipsychotic drug suggests that this technology can be broadly used for cell-type-specific drug profiling and for the study of drug-methylome interactions.
| S-EPMC6023403 | biostudies-literature