scholarly journals Methylation pattern of nc886 in non-human mammals

2021 ◽  
Author(s):  
Daria Kostiniuk ◽  
Hely Tamminen ◽  
Pashupati Mishra ◽  
Saara Marttila ◽  
Emma Raitoharju
Keyword(s):  
Dna Methylation ◽  
Animal Models ◽  
Guinea Pigs ◽  
Methylation Status ◽  
Great Apes ◽  
Methylation Pattern ◽  
Old World Monkeys ◽  
Methylation Data ◽  
Old World ◽  
Metastable Epiallele

Background: In humans, the nc886 locus is a polymorphically imprinted metastable epiallele. Periconceptional conditions have an effect on the methylation status of nc886, and further, this methylation status is associated with health outcomes in later life, in line with the Developmental Origins of Health and Disease (DOHaD) hypothesis. Animal models would offer opportunities to study the associations between periconceptional conditions, nc886 methylation status and metabolic phenotypes further. Thus, we set out to investigate the methylation pattern of the nc886 locus in non-human mammals. Data: We obtained DNA methylation data from the data repository GEO for mammals, whose nc886 gene included all three major parts of nc886 and had sequency similarity of over 80% with the human nc886. Our final sample set consisted of DNA methylation data from humans, chimpanzees, bonobos, gorillas, orangutangs, baboons, macaques, vervets, marmosets and guinea pigs. Results: In human data sets the methylation pattern of nc886 locus followed the expected bimodal distribution, indicative of polymorphic imprinting. In great apes, we identified a unimodal DNA methylation pattern with 50% methylation level in all individuals and in all subspecies. In Old World monkeys, the between individual variation was greater and methylation on average was close to 60%. In guinea pigs the region around the nc886 homologue was non-methylated. Results obtained from the sequence comparison of the CTCF binding sites flanking the nc886 gene support the results on the DNA methylation data. Conclusions: Our results indicate that unlike in humans, nc886 is not a polymorphically imprinted metastable epiallele in non-human primates or in guinea pigs, thus implying that animal models are not applicable for nc886 research. The obtained data suggests that the nc886 region may be classically imprinted in great apes, and potentially also in Old World monkeys, but not in guinea pigs.

scholarly journals DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Sasaki ◽  
Margaret E. Eng ◽  
Abigail H. Lee ◽  
Alisa Kostaki ◽  
Stephen G. Matthews
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Guinea Pigs ◽  
Critical Role ◽  
Methylation Status ◽  
Peripheral Tissues ◽  
Epigenetic Biomarkers ◽  
Differentially Methylated Genes ◽  
Increased Risk ◽  
Synthetic Glucocorticoids

AbstractSynthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

scholarly journals Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Saara Marttila ◽  
Leena E. Viiri ◽  
Pashupati P. Mishra ◽  
Brigitte Kühnel ◽  
Pamela R. Matias-Garcia ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Methylation Status ◽  
Induced Pluripotent Stem Cell ◽  
Methylation Pattern ◽  
Rna Expression ◽  
Non Coding Rna ◽  
Mother’S Age ◽  
Induced Pluripotent ◽  
Metastable Epiallele

Abstract Background Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines. Results We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual’s methylation status is associated with the mother’s age and socioeconomic status, but not with the individual’s own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood. Conclusions These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.

Cortical Orofacial Motor Representation in Old World Monkeys, Great Apes, and Humans

2004 ◽  
Vol 63 (2) ◽  
pp. 82-106 ◽  
Author(s):  
Chet C. Sherwood ◽  
Ralph L. Holloway ◽  
Joseph M. Erwin ◽  
Patrick R. Hof
Keyword(s):  
Great Apes ◽  
Old World Monkeys ◽  
Motor Representation ◽  
Old World

EPCO-01. MOLECULAR PROFILING OF SPINAL CORD EPENDYMOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi1-vi1
Author(s):  
Erika Yamazawa ◽  
Shota Tanaka ◽  
Genta Nagae ◽  
Takayoshi Umeda ◽  
Taijun Hana ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dna Methylation ◽  
Methylation Status ◽  
Neurofibromatosis Type ◽  
Methylation Pattern ◽  
Who Grade ◽  
Spinal Ependymoma ◽  
Fresh Frozen ◽  
Spinal Cord Ependymoma ◽  
The Difference

Abstract BACKGROUND Ependymomas are currently classified into 9 subgroups by DNA methylation profiles. Although spinal cord ependymoma (SP-EPN) is distinct from other tumors, diversity within SP-EPN is still unclear. Here, we used transcriptomic and epigenomic profiles to investigate the diversity among Japanese SP-EPN cases. MATERIALS AND METHODS We analyzed 57 SP-EPN patients (32 males and 25 females, aged from 18 to 78 years, median: 52), including two cases of neurofibromatosis type 2, five cases of grade 3 (WHO grade). We obtained transcriptome (RNA-seq) and DNA methylation (Infinium Methylation EPIC array) data from fresh frozen specimens of SP-EPN resected at the University of Tokyo Hospital and our collaborative groups. RESULTS Three cases had a previous intracranial ependymoma operation. Hierarchical clustering of the DNA methylation data showed that these three cases of intracranial origin as a different cluster from spinal origin. The 45 grade 2 spinal ependymoma showed a relatively homogenous methylation pattern. However, the methylation status of HOX gene cluster regions is compatible with the segment of origin, which reflects the cells of origins are derived after the determination of segment identity. RNA sequencing of 57 cases revealed two subgroups within grade 2. Gene ontology analysis of differentially expressed genes suggested the difference in metabolic state such as rRNA translation and mitochondrial respiration between the two expression subgroups. CONCLUSION Epigenetic analysis indicated the accurate body segment origin of SP-EPN. We observed that metabolic states could divide grade 2 spinal cord ependymoma into 2 subgroups and will present the relationship to clinicopathological information.

scholarly journals The Expression Level of mRNA, Protein, and DNA Methylation Status of FOSL2 of Uyghur in XinJiang in Type 2 Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jun Li ◽  
Siyuan Li ◽  
Ying Hu ◽  
Guolei Cao ◽  
Siyao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Methylation Status ◽  
Methylation Data ◽  
Biochemical Indicators ◽  
Expression Levels ◽  
Protein Levels ◽  
Cpg Sites

Objective. We investigated the expression levels of both FOSL2 mRNA and protein as well as evaluating DNA methylation in the blood of type 2 diabetes mellitus (T2DM) Uyghur patients from Xinjiang. This study also evaluated whether FOSL2 gene expression had demonstrated any associations with clinical and biochemical indicators of T2DM. Methods. One hundred Uyghur subjects where divided into two groups, T2DM and nonimpaired glucose tolerance (NGT) groups. DNA methylation of FOSL2 was also analyzed by MassARRAY Spectrometry and methylation data of individual units were generated by the EpiTyper v1.0.5 software. The expression levels of FOS-like antigen 2 (FOSL2) and the protein expression levels were analyzed. Results. Significant differences were observed in mRNA and protein levels when compared with the NGT group, while methylation rates of eight CpG units within the FOSL2 gene were higher in the T2DM group. Methylation of CpG sites was found to inversely correlate with expression of other markers. Conclusions. Results show that a correlation between mRNA, protein, and DNA methylation of FOSL2 gene exists among T2DM patients from Uyghur. FOSL2 protein and mRNA were downregulated and the DNA became hypermethylated, all of which may be involved in T2DM pathogenesis in this population.

Sequence divergence, polymorphism and evolution of the middle-wave and long-wave visual pigment genes of great apes and old world monkeys

1994 ◽  
Vol 34 (19) ◽  
pp. 2483-2491 ◽  
Author(s):  
Kanwaljit S. Dulai ◽  
James K. Bowmaker ◽  
John D. Mollon ◽  
David M. Hunt
Keyword(s):  
Visual Pigment ◽  
Sequence Divergence ◽  
Great Apes ◽  
Old World Monkeys ◽  
Old World ◽  
Long Wave ◽  
Pigment Genes

scholarly journals Signatures of polycomb repression and reduced H3K4 trimethylation are associated with p15INK4b DNA methylation in AML

Blood ◽  
2010 ◽  
Vol 115 (15) ◽  
pp. 3098-3108 ◽  
Author(s):  
Thomas A. Paul ◽  
Juraj Bies ◽  
Donald Small ◽  
Linda Wolff
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Transcriptional Repression ◽  
Trichostatin A ◽  
Methylation Status ◽  
Suppressor Gene ◽  
Methylation Pattern ◽  
Dna Hypermethylation ◽  
Polycomb Repression ◽  
On Chip

Abstract DNA hypermethylation of the p15INK4b tumor suppressor gene is commonly observed in acute myeloid leukemia (AML). Repressive histone modifications and their associated binding proteins have been implicated in the regulation of DNA methylation and the transcriptional repression of genes with DNA methylation. We have used high-density chromatin immunoprecipitation-on-chip to determine the histone modifications that normally regulate p15INK4b expression in AML cells and how these marks are altered in cells that have p15INK4b DNA methylation. In AML patient blasts without p15INK4b DNA methylation, a bivalent pattern of active (H3K4me3) and repressive (H3K27me3) modifications exist at the p15INK4b promoter. AML patient blasts with p15INK4b DNA methylation lose H3K4me3 at p15INK4b and become exclusively marked by H3K27me3. H3K27me3, as well as EZH2, extends throughout p14ARF and p16INK4a, indicating that polycomb repression of p15INK4b is a common feature in all AML blasts irrespective of the DNA methylation status of the gene. Reactivation of p15INK4b expression in AML cell lines and patient blasts using 5-aza-2′-deoxycytidine (decitabine) and trichostatin A increased H3K4me3 and maintained H3K27me3 enrichment at p15INK4b. These data indicate that AML cells with p15INK4b DNA methylation have an altered histone methylation pattern compared with unmethylated samples and that these changes are reversible by epigenetic drugs.

scholarly journals Deoxyribonucleic Acid Methylation Controls Cell Type-Specific Expression of Steroidogenic Factor 1

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5599-5609 ◽  
Author(s):  
Erling A. Hoivik ◽  
Linda Aumo ◽  
Reidun Aesoy ◽  
Haldis Lillefosse ◽  
Aurélia E. Lewis ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rna Polymerase Ii ◽  
Methylation Status ◽  
Endocrine System ◽  
Methylation Pattern ◽  
Proximal Promoter ◽  
Specific Expression ◽  
Steroidogenic Factor 1 ◽  
In Cells

Steroidogenic factor 1 (SF1) is expressed in a time- and cell-specific manner in the endocrine system. In this study we present evidence to support that methylation of CpG sites located in the proximal promoter of the gene encoding SF1 contributes to the restricted expression pattern of this nuclear receptor. DNA methylation analyses revealed a nearly perfect correlation between the methylation status of the proximal promoter and protein expression, such that it was hypomethylated in cells that express SF1 but hypermethylated in nonexpressing cells. Moreover, in vitro methylation of this region completely repressed reporter gene activity in transfected steroidogenic cells. Bisulfite sequencing of DNA from embryonic tissue demonstrated that the proximal promoter was unmethylated in the developing testis and ovary, whereas it was hypermethylated in tissues that do not express SF1. Together these results indicate that the DNA methylation pattern is established early in the embryo and stably inherited thereafter throughout development to confine SF1 expression to the appropriate tissues. Chromatin immunoprecipitation analyses revealed that the transcriptional activator upstream stimulatory factor 2 and RNA polymerase II were specifically recruited to this DNA region in cells in which the proximal promoter is hypomethylated, providing functional support for the fact that lack of methylation corresponds to a transcriptionally active gene. In conclusion, we identified a region within the SF1/Sf1 gene that epigenetically directs cell-specific expression of SF1.

scholarly journals Intertwining of paleontology and medicine: implications for structure-function relationships, behavior, and habitat in paleontology

1992 ◽  
Vol 6 ◽  
pp. 252-252
Author(s):  
Bruce Rothschild
Keyword(s):  
Infectious Agent ◽  
Great Apes ◽  
Definitive Diagnosis ◽  
Old World Monkeys ◽  
Old World ◽  
Sexually Transmitted ◽  
School Of Medicine ◽  
Depth Analysis ◽  
Unique Model ◽  
Genetic And Environmental Factors

Medicine and paleontology have been intertwined from the start. Gideon Algernon Mantell, a family physician from Sussex, and his wife, while on patient care “rounds,” found the first English dinosaur. Nineteen years later in 1841, Sir Richard Owen established the neologism, dinosaur, to categorize these animals. It is not accidental that the first Dean of Kansas University School of Medicine was also the founder of the University's Museum of Natural History. Rheumatology and paleontology paths have also crossed in the form of Thinocetus arthritus, so named because the ligamentous fusion in a specimen mistaken for arthritis.Technology and understanding of disease processes have advanced sufficiently to allow hypotheses to be critically examined. The underlying assumptions are that:1. Disease manifestations are relatively stable through time.2. Tissue is preserved in a state amenable to analysis.3. Pathology can be distinguished from diagenesis (pseudopathology).4. Analysis of pathology as a skeletal phenomenon provides more insight than examination of isolated bones.5. Analysis of pathology as a population phenomenon provides more insight than examination of isolated skeletons.Exemplifying the intertwining nature of the fields is the presence of spine and sacroiliac involvement and the nature and distribution of erosive lesions in the great apes (Gorilla and Pan (chimpanzee), the lesser ape (Hylobates) and Old World monkeys (Theropithecus, Papio, Cercopithecus, Macaca, Presbytis, Colobus, and Erythrocebus). This allowed definitive diagnosis of spondyloarthropathy. Reproducibility of diseases across species lines has been established for spondyloarthropathy (gorilla, chimp, monkey), not only for gross or radiologic appearance of individual bones, but also for skeletal distribution. More recently, similar observations have been made for Smilodon and Mammuthus. Reactive arthritis, related to infectious agent diarrhea or sexually transmitted, is a consideration. Infectious agent diarrhea is common in Old World primates. This natural disease state provides a unique model system for in depth analysis of the contribution of genetic and environmental factors to disease pathophysiology.

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