The differentially methylated region ofMEG8is hypermethylated in patients with Temple syndrome

Epigenomics ◽  
2015 ◽  
Vol 7 (7) ◽  
pp. 1089-1097 ◽  
Author(s):  
Susanne Bens ◽  
Julia Kolarova ◽  
Gabriele Gillessen-Kaesbach ◽  
Karin Buiting ◽  
Jasmin Beygo ◽  
...  
Keyword(s):  
Differentially Methylated Region ◽  
Temple Syndrome

scholarly journals Transcriptomic and epigenomic remodeling occurs during vascular cambium periodicity in Populus tomentosa

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Bo Chen ◽  
Huimin Xu ◽  
Yayu Guo ◽  
Paul Grünhofer ◽  
Lukas Schreiber ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Plant Hormone ◽  
Target Genes ◽  
Populus Tomentosa ◽  
Differentially Expressed ◽  
Vascular Cambium ◽  
Differentially Methylated Region ◽  
Gene Body Methylation ◽  
Transcription Analysis ◽  
Global Methylation

AbstractTrees in temperate regions exhibit evident seasonal patterns, which play vital roles in their growth and development. The activity of cambial stem cells is the basis for regulating the quantity and quality of wood, which has received considerable attention. However, the underlying mechanisms of these processes have not been fully elucidated. Here we performed a comprehensive analysis of morphological observations, transcriptome profiles, the DNA methylome, and miRNAs of the cambium in Populus tomentosa during the transition from dormancy to activation. Anatomical analysis showed that the active cambial zone exhibited a significant increase in the width and number of cell layers compared with those of the dormant and reactivating cambium. Furthermore, we found that differentially expressed genes associated with vascular development were mainly involved in plant hormone signal transduction, cell division and expansion, and cell wall biosynthesis. In addition, we identified 235 known miRNAs and 125 novel miRNAs. Differentially expressed miRNAs and target genes showed stronger negative correlations than other miRNA/target pairs. Moreover, global methylation and transcription analysis revealed that CG gene body methylation was positively correlated with gene expression, whereas CHG exhibited the opposite trend in the downstream region. Most importantly, we observed that the number of CHH differentially methylated region (DMR) changes was the greatest during cambium periodicity. Intriguingly, the genes with hypomethylated CHH DMRs in the promoter were involved in plant hormone signal transduction, phenylpropanoid biosynthesis, and plant–pathogen interactions during vascular cambium development. These findings improve our systems-level understanding of the epigenomic diversity that exists in the annual growth cycle of trees.

scholarly journals Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 544
Author(s):  
Tien-Chi Huang ◽  
Kung-Chao Chang ◽  
Jen-Yun Chang ◽  
Yi-Shan Tsai ◽  
Yao-Jong Yang ◽  
...  
Keyword(s):  
Maternal Effect ◽  
Hydatidiform Mole ◽  
Placental Tissue ◽  
Differentially Methylated Region ◽  
Normal Birth ◽  
Maternal Effect Genes ◽  
Common Etiology ◽  
Artificial Abortion ◽  
Secondary Dmr ◽  
Placental Mesenchymal Dysplasia

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

scholarly journals Somatotroph Tumors and the Epigenetic Status of the GNAS Locus

2021 ◽  
Vol 22 (14) ◽  
pp. 7570
Author(s):  
Pauline Romanet ◽  
Justine Galluso ◽  
Peter Kamenicky ◽  
Mirella Hage ◽  
Marily Theodoropoulou ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Somatostatin Analogues ◽  
Differentially Methylated Region ◽  
Monoallelic Expression ◽  
Lower Sensitivity ◽  
Biallelic Expression ◽  
Expression Levels ◽  
Methylation Index ◽  
Significant Difference ◽  
Gsp Oncogene

Background: Forty percent of somatotroph tumors harbor recurrent activating GNAS mutations, historically called the gsp oncogene. In gsp-negative somatotroph tumors, GNAS expression itself is highly variable; those with GNAS overexpression most resemble phenotypically those carrying the gsp oncogene. GNAS is monoallelically expressed in the normal pituitary due to methylation-based imprinting. We hypothesize that changes in GNAS imprinting of gsp-negative tumors affect GNAS expression levels and tumorigenesis. Methods: We characterized the GNAS locus in two independent somatotroph tumor cohorts: one of 23 tumors previously published (PMID: 31883967) and classified by pan-genomic analysis, and a second with 82 tumors. Results: Multi-omics analysis of the first cohort identified a significant difference between gsp-negative and gsp-positive tumors in the methylation index at the known differentially methylated region (DMR) of the GNAS A/B transcript promoter, which was confirmed in the larger series of 82 tumors. GNAS allelic expression was analyzed using a polymorphic Fok1 cleavage site in 32 heterozygous gsp-negative tumors. GNAS expression was significantly reduced in the 14 tumors with relaxed GNAS imprinting and biallelic expression, compared to 18 tumors with monoallelic expression. Tumors with relaxed GNAS imprinting showed significantly lower SSTR2 and AIP expression levels. Conclusion: Altered A/B DMR methylation was found exclusively in gsp-negative somatotroph tumors. 43% of gsp-negative tumors showed GNAS imprinting relaxation, which correlated with lower GNAS, SSTR2 and AIP expression, indicating lower sensitivity to somatostatin analogues and potentially aggressive behavior.

scholarly journals Mosaic Segmental and Whole-Chromosome upd(11)mat in Silver-Russell Syndrome

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 581
Author(s):  
Laura Pignata ◽  
Angela Sparago ◽  
Orazio Palumbo ◽  
Elena Andreucci ◽  
Elisabetta Lapi ◽  
...  
Keyword(s):  
Molecular Level ◽  
Opposite Sign ◽  
Uniparental Disomy ◽  
Differentially Methylated Region ◽  
Imprinted Genes ◽  
Loss Of Function ◽  
Growth Disturbances ◽  
Molecular Defects ◽  
Entire Chromosome ◽  
Silver Russell Syndrome

Molecular defects altering the expression of the imprinted genes of the 11p15.5 cluster are responsible for the etiology of two congenital disorders characterized by opposite growth disturbances, Silver–Russell syndrome (SRS), associated with growth restriction, and Beckwith–Wiedemann syndrome (BWS), associated with overgrowth. At the molecular level, SRS and BWS are characterized by defects of opposite sign, including loss (LoM) or gain (GoM) of methylation at the H19/IGF2:intergenic differentially methylated region (H19/IGF2:IG-DMR), maternal or paternal duplication (dup) of 11p15.5, maternal (mat) or paternal (pat) uniparental disomy (upd), and gain or loss of function mutations of CDKN1C. However, while upd(11)pat is found in 20% of BWS cases and in the majority of them it is segmental, upd(11)mat is extremely rare, being reported in only two SRS cases to date, and in both of them is extended to the whole chromosome. Here, we report on two novel cases of mosaic upd(11)mat with SRS phenotype. The upd is mosaic and isodisomic in both cases but covers the entire chromosome in one case and is restricted to 11p14.1-pter in the other case. The segmental upd(11)mat adds further to the list of molecular defects of opposite sign in SRS and BWS, making these two imprinting disorders even more specular than previously described.

scholarly journals “mir152 hypomethylation, potentially triggered by embryonic hypoxia, as a common mechanism for non-syndromic cleft lip/palate”

2019 ◽  
Author(s):  
Lucas Alvizi ◽  
Luciano Abreu Brito ◽  
Bárbara Bischain ◽  
Camila Bassi Fernandes da Silva ◽  
Sofia Ligia Guimaraes Ramos ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Differentially Methylated Region ◽  
Common Mechanism ◽  
Craniofacial Malformations ◽  
Predisposing Factor ◽  
Complex Disorder ◽  
Cleft Lip Palate ◽  
Functional Investigation

AbstractNon-syndromic cleft lip/palate (NSCLP), the most common human craniofacial malformations, is a complex disorder given its genetic heterogeneity and multifactorial component revealed by genetic, epidemiological and epigenetic findings. Association of epigenetic variations with NSCLP has been made, however still of little functional investigation. Here we combined a reanalysis of NSCLP methylome data with genetic analysis and used both in vitro and in vivo approaches to dissect the functional effects of epigenetic changes. We found a frequent differentially methylated region in mir152, hypomethylated in NSCLP cohorts (21-26%), leading to mir152 overexpression. In vivo analysis using zebrafish embryos revealed that mir152 upregulation leads to craniofacial impairment analogue to palatal defects. Also, we demonstrated that zebrafish embryonic hypoxia leads to mir152 upregulation combined with mir152 hypomethylation and also analogue palatal alterations. We therefore suggest mir152 hypomethylation, potentially induced by hypoxia in early development, as a novel and frequent predisposing factor to NSCLP.

scholarly journals Oocyte age and preconceptual alcohol use are highly correlated with epigenetic imprinting of a noncoding RNA (nc886)

2021 ◽  
Vol 118 (12) ◽  
pp. e2026580118
Author(s):  
Brittany L. Carpenter ◽  
Tanaka K. Remba ◽  
Stacey L. Thomas ◽  
Zachary Madaj ◽  
Lucy Brink ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Cigarette Smoking ◽  
Noncoding Rna ◽  
Environmental Influence ◽  
Differentially Methylated Region ◽  
Older Mothers ◽  
Environmental Perturbations ◽  
Human Genes ◽  
Apparent Relationship ◽  
Highly Correlated

Genomic imprinting occurs before fertilization, impacts every cell of the developing child, and may be sensitive to environmental perturbations. The noncoding RNA, nc886 (also called VTRNA2-1) is the only known example of the ∼100 human genes imprinted by DNA methylation, that shows polymorphic imprinting in the population. The nc886 gene is part of an ∼1.6-kb differentially methylated region (DMR) that is methylated in the oocyte and silenced on the maternal allele in about 75% of humans worldwide. Here, we show that the presence or absence of imprinting at the nc886 DMR in an individual is consistent across different tissues, confirming that the imprint is established before cellular differentiation and is maintained into adulthood. We investigated the relationships between the frequency of imprinting in newborns and maternal age, alcohol consumption and cigarette smoking before conception in more than 1,100 mother/child pairs from South Africa. The probability of imprinting in newborns was increased in older mothers and decreased in mothers who drank alcohol before conception. On the other hand, cigarette smoking had no apparent relationship with the frequency of imprinting. These data show an epigenetic change during oocyte maturation which is potentially subject to environmental influence. Much focus has been placed on avoiding alcohol consumption during pregnancy, but our data suggest that drinking before conception may affect the epigenome of the newborn.

scholarly journals A Radiosensitivity Gene Signature and PD-L1 Status Predict Clinical Outcome of Patients with Glioblastoma Multiforme in The Cancer Genome Atlas Dataset

2020 ◽  
Vol 52 (2) ◽  
pp. 530-542 ◽  
Author(s):  
Bum-Sup Jang ◽  
In Ah Kim
Keyword(s):  
Gene Signature ◽  
Mapk Signaling ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Mitogen Activated Protein Kinase ◽  
Differentially Methylated Region ◽  
Immune Repertoire ◽  
Programmed Death ◽  
Cancer Genome Atlas ◽  
Genome Atlas

PurposeCombination of radiotherapy and immune checkpoint blockade such as programmed death- 1 (PD-1) or programmed death-ligand 1 (PD-L1) blockade is being actively tested in clinical trial. We aimed to identify a subset of patients that could potentially benefit from this strategy using The Cancer Genome Atlas (TCGA) dataset for glioblastoma (GBM).Materials and MethodsA total of 399 cases were clustered into radiosensitive versus radioresistant (RR) groups based on a radiosensitivity gene signature and were also stratified as PD-L1 high versus PD-L1 low groups by expression of CD274 mRNA. Differential and integrated analyses with expression and methylation data were performed. CIBERSORT was used to enumerate the immune repertoire that resulted from transcriptome profiles.ResultsWe identified a subset of GBM, PD-L1-high-RR group which showed worse survival compared to others. In PD-L1-high-RR, differentially expressed genes (DEG) were highly enriched for immune response and mapped into activation of phosphoinositide 3-kinase–AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Integration of DEG and differentially methylated region identified that the kinase MAP3K8-involved in T-cell receptor signaling was upregulated and BAI1, a factor which inhibits angiogenesis, was silenced. CIBERSORT showed that a higher infiltration of the immune repertoire, which included M2 macrophages and regulatory T cells.ConclusionTaken together, PD-L1-high-RR group could potentially benefit from radiotherapy combined with PD-1/PD-L1 blockade and angiogenesis inhibition.

scholarly journals The H19 Differentially Methylated Region Marks the Parental Origin of a Heterologous Locus without Gametic DNA Methylation

2004 ◽  
Vol 24 (9) ◽  
pp. 3588-3595 ◽  
Author(s):  
Kye-Yoon Park ◽  
Elizabeth A. Sellars ◽  
Alexander Grinberg ◽  
Sing-Ping Huang ◽  
Karl Pfeifer
Keyword(s):  
Dna Methylation ◽  
Mouse Chromosome ◽  
Germ Line ◽  
Transcriptional Silencing ◽  
Chromosome 7 ◽  
Differentially Methylated Region ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Chromosome 5 ◽  
The Third

ABSTRACT Igf2 and H19 are coordinately regulated imprinted genes physically linked on the distal end of mouse chromosome 7. Genetic analyses demonstrate that the differentially methylated region (DMR) upstream of the H19 gene is necessary for three distinct functions: transcriptional insulation of the maternal Igf2 allele, transcriptional silencing of paternal H19 allele, and marking of the parental origin of the two chromosomes. To test the sufficiency of the DMR for the third function, we inserted DMR at two heterologous positions in the genome, downstream of H19 and at the alpha-fetoprotein locus on chromosome 5. Our results demonstrate that the DMR alone is sufficient to act as a mark of parental origin. Moreover, this activity is not dependent on germ line differences in DMR methylation. Thus, the DMR can mark its parental origin by a mechanism independent of its own DNA methylation.

scholarly journals Pseudohypoparathyroidism type 1a with hypomethylation at the responsible differentially methylated region for Beckwith-Wiedemann syndrome

2015 ◽  
Vol 2015 (S1) ◽  
Author(s):  
Yoshiaki Ohtsu ◽  
Kanako Kurata ◽  
Mai Takahashi ◽  
Takanori Kowase ◽  
Hirokazu Arakawa ◽  
...  
Keyword(s):  
Differentially Methylated Region
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