scholarly journals Transcription-dependent DNA methylation at the imprinted Zrsr1-DMR

2018 ◽  
Author(s):  
Keiichiro Joh
Keyword(s):  
Dna Methylation ◽  
Opposite Direction ◽  
Adult Brain ◽  
Differentially Methylated Region ◽  
Imprinted Gene ◽  
Maternal Expression ◽  
First Intron

AbstractZrsr1 is a paternally expressed imprinted gene located in the first intron of Commd1, and the Zrsr1 promoter resides in a differentially methylated region (DMR) that is maternally methylated in the oocyte. However, a mechanism for the establishment of the methylation has remained obscure. Commd1 is transcribed in the opposite direction to Zrsr1 with predominant maternal expression, especially in the adult brain. In this study, we found Commed1 transcribed through the DMR in the growing oocyte. Zrsr1-DMR methylation was abolished by the prevention of Commd1 transcription. This result indicated that methylation at the Zrsr1-DMR was transcription-dependent.

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 DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions

2018 ◽  
Vol 143 (3) ◽  
pp. 552-560 ◽  
Author(s):  
Ayodele Gomih ◽  
Jennifer S. Smith ◽  
Kari E. North ◽  
Michael G. Hudgens ◽  
Wendy R. Brewster ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Low Grade ◽  
Gene Control ◽  
Cervical Lesions ◽  
Imprinted Gene ◽  
Control Regions

scholarly journals Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2839-2846 ◽  
Author(s):  
Svenja Steinfelder ◽  
Stefan Floess ◽  
Dirk Engelbert ◽  
Barbara Haeringer ◽  
Udo Baron ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Transcriptional Activity ◽  
Epigenetic Modification ◽  
Cell Receptor ◽  
Noncoding Region ◽  
Differentially Methylated Region

Abstract CCR6 is a chemokine receptor expressed on Th17 cells and regulatory T cells that is induced by T-cell priming with certain cytokines, but how its expression and stability are regulated at the molecular level is largely unknown. Here, we identified and characterized a noncoding region of the human CCR6 locus that displayed unmethylated CpG motifs (differentially methylated region [DMR]) selectively in CCR6+ lymphocytes. CCR6 expression on circulating CD4+ T cells was stable on cytokine-induced proliferation but partially down-regulated on T-cell receptor stimulation. However, CCR6 down-regulation was mostly transient, and the DMR within the CCR6 locus remained demethylated. Notably, in vitro induction of CCR6 expression with cytokines in T-cell receptor-activated naive CD4+ T cells was not associated with a demethylated DMR and resulted in unstable CCR6 expression. Conversely, treatment with the DNA methylation inhibitor 5′-azacytidine induced demethylation of the DMR and led to increased and stable CCR6 expression. Finally, when cloned into a reporter gene plasmid, the DMR displayed transcriptional activity in memory T cells that was suppressed by DNA methylation. In summary, we have identified a noncoding region of the human CCR6 gene with methylation-sensitive transcriptional activity in CCR6+ T cells that controls stable CCR6 expression via epigenetic mechanisms.

Sperm DNA methylation of H19 imprinted gene and male infertility

Andrologia ◽  
2017 ◽  
Vol 49 (10) ◽  
pp. e12766 ◽  
Author(s):  
F. Nasri ◽  
B. Gharesi-Fard ◽  
B. Namavar Jahromi ◽  
M. A. Farazi-fard ◽  
M. Banaei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Male Infertility ◽  
Imprinted Gene ◽  
Sperm Dna ◽  
Sperm Dna Methylation

scholarly journals Imprinted gene expression in the rat embryo–fetal axis is altered in response to periconceptional maternal low protein diet

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 265-277 ◽  
Author(s):  
Wing Yee Kwong ◽  
Daniel J Miller ◽  
Elizabeth Ursell ◽  
Arthur E Wild ◽  
Adrian P Wilkins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Mrna Level ◽  
Postnatal Growth ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Differentially Methylated Region ◽  
Imprinted Gene ◽  
Low Protein ◽  
Gender Specific

In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0–4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) inH19mRNA level. A significant reduction inH19(9.4%) andIgf2(10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression ofIgf2Rwas observed in relation to maternal diet. The reduction inH19mRNA expression did not correlate with an observed alteration in DNA methylation at theH19differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or femaleH19andIgf2imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affectedH19andIgf2imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself.

Effect of vitrification on in vitro development and imprinted gene Grb10 in mouse embryos

Reproduction ◽  
2017 ◽  
Vol 154 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Jianfeng Yao ◽  
Lixia Geng ◽  
Rongfu Huang ◽  
Weilin Peng ◽  
Xuan Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cpg Island ◽  
Formation Rate ◽  
Mouse Embryos ◽  
Major Type ◽  
Hatching Rate ◽  
Preimplantation Embryo Development ◽  
Imprinted Gene

Vitrification of embryos is a routine procedure in IVF (in vitrofertilization) laboratories. In the present study, we aimed to investigate the effect of vitrification on mouse preimplantation embryo developmentin vitro, and effect on the epigenetic status of imprinted geneGrb10in mouse embryos. The blastocyst formation rate for vitrified 8-cell embryos was similar to the non-vitrified 8-cell embryos, whereas the blastocyst hatching rate was lower than that of the non-vitrified group. The expression level ofGrb10major-type transcript decreased significantly in vitrified blastocysts compared with non-vitrified andin vivoblastocysts. Moreover, the global DNA methylation level in 8-cell embryos and blastocysts, and the DNA methylation at CpG island 1 (CGI1) ofGrb10in blastocysts were also significantly decreased after vitrification.In vitroculture condition had no adverse effect, except for on the DNA methylation inGrb10CGI1. These results suggest that vitrification may reduce thein vitrodevelopment of mouse 8-cell embryos and affect the expression and DNA methylation of imprinted geneGrb10.

scholarly journals IL-10 Production By CLL Cells Is Enhanced in the Anergic IGHV Mutated Subset and Associates with Reduced DNA Methylation of the IL-10 Locus

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2917-2917
Author(s):  
Samantha Drennan ◽  
Annalisa D'Avola ◽  
Yifang Gao ◽  
Eleni Chrysostomou ◽  
Andrew J Steele ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Locus ◽  
Conflicts Of Interest ◽  
Methylation Status ◽  
Differentially Methylated Region ◽  
Variable Degree ◽  
Immunoglobulin Gene ◽  
Transcript Levels ◽  
Low Levels ◽  
B10 Cells

Abstract The B-cell receptor (BCR) of chronic lymphocytic leukemia (CLL) cells with unmutated (U-CLL) or mutated (M-CLL) immunoglobulin gene heavy-chain variable (IGHV) regions shows a variable degree of anergy, associated with low surface IgM (sIgM) levels and signaling capacity, more evident in M-CLL. DNA methylation is also different between M-CLL and U-CLL. Patients from both subsets are immunosuppressed from the early stages, possibly influenced by the ability of activated CLL cells to produce IL-10, a property of B10 cells. The aim of this study was to investigate associations between capacity of circulating CLL cells to differentiate into B10 cells and features of anergy. In parallel, the methylation status of the IL-10 gene locus was probed in order to investigate associations between IL-10 gene methylation and production. CLL cells were isolated and cultured +/- TLR9 activation with CpG (ODN-2006). Cytokine secretion was measured in supernatants (Luminex) and IL10 transcript was measured (RT-qPCR) from cell pellets. IL-10 production by CLL cells was measured by intracellular flow cytometry following stimulation with CpG for 24 hours. Epigenetic profiling was performed using MassARRAY and the 450K Array. We found that activation of CLL cells by CpG consistently induced production and secretion of IL-10 protein, while no or low amounts of pro-inflammatory cytokines were detected. Production of IL-10 was significantly higher in M-CLL than in U-CLL. Levels also correlated with lower sIgM levels and signaling capacity, both features of anergy. A linear correlation was present between secretion, intracellular production and transcript levels of IL-10, suggesting no aberrant post-transcriptional controls. In the absence of CpG activation, IL-10 transcript levels were also detected at low levels in M-CLL, while they were even lower in U-CLL. To identify a potential basis for the differential expression, DNA methylation analysis of IL-10 gene locus was performed. While the promoter region displayed similarly low levels of methylation in both U-CLL and M-CLL, methylation differences were detected immediately downstream of the promoter within the first intron (approximately +200 to +500 bp, differentially methylated region 1, DMR1) and in the gene body (approximately +1300 to +1800 bp, DMR2). Both DMR1 and DMR2 were markedly more hypomethylated in M-CLL than U-CLL, with the greatest difference detected at cg17067005 within DMR1. Each of these regions display histone H3 lysine 27 acetylation (H3K27ac) in B cells (GM12878 cells), thus are likely to represent functional DNA elements. Analysis of IL-10 transcript levels with methylation demonstrated a mutually exclusive pattern between expression and methylation of both DMR1 and DMR2. These data document a strong link between capacity to differentiate into B10-like cells and anergy, and suggest an epigenetic component in the regulation of IL-10 production in CLL cells. This capacity may contribute to immunosuppression. While U-CLL appears less able to produce IL-10 on a per cell basis, higher tumor load may compensate, accounting for clinical immunosuppression in both subsets. Disclosures No relevant conflicts of interest to declare.

scholarly journals CTCF modulates allele-specific sub-TAD organization and imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
David Llères ◽  
Benoît Moindrot ◽  
Rakesh Pathak ◽  
Vincent Piras ◽  
Mélody Matelot ◽  
...  
Keyword(s):  
Gene Activation ◽  
Three Dimensional ◽  
Ctcf Binding ◽  
Differentially Methylated Region ◽  
Ctcf Binding Site ◽  
Mammalian Development ◽  
Imprinted Gene ◽  
Maternal Chromosome ◽  
Additional Layer ◽  
Allele Specific

Abstract Background Genomic imprinting is essential for mammalian development and provides a unique paradigm to explore intra-cellular differences in chromatin configuration. So far, the detailed allele-specific chromatin organization of imprinted gene domains has mostly been lacking. Here, we explored the chromatin structure of the two conserved imprinted domains controlled by paternal DNA methylation imprints—the Igf2-H19 and Dlk1-Dio3 domains—and assessed the involvement of the insulator protein CTCF in mouse cells. Results Both imprinted domains are located within overarching topologically associating domains (TADs) that are similar on both parental chromosomes. At each domain, a single differentially methylated region is bound by CTCF on the maternal chromosome only, in addition to multiple instances of bi-allelic CTCF binding. Combinations of allelic 4C-seq and DNA-FISH revealed that bi-allelic CTCF binding alone, on the paternal chromosome, correlates with a first level of sub-TAD structure. On the maternal chromosome, additional CTCF binding at the differentially methylated region adds a further layer of sub-TAD organization, which essentially hijacks the existing paternal-specific sub-TAD organization. Perturbation of maternal-specific CTCF binding site at the Dlk1-Dio3 locus, using genome editing, results in perturbed sub-TAD organization and bi-allelic Dlk1 activation during differentiation. Conclusions Maternal allele-specific CTCF binding at the imprinted Igf2-H19 and the Dlk1-Dio3 domains adds an additional layer of sub-TAD organization, on top of an existing three-dimensional configuration and prior to imprinted activation of protein-coding genes. We speculate that this allele-specific sub-TAD organization provides an instructive or permissive context for imprinted gene activation during development.

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease

2020 ◽  
Author(s):  
Ashani Lecamwasam ◽  
Boris Novakovic ◽  
Braydon Meyer ◽  
Elif I Ekinci ◽  
Karen M Dwyer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Secretory Protein ◽  
Differentially Methylated Region ◽  
P Value ◽  
Operating Characteristics ◽  
Cross Sectional ◽  
Cpg Sites ◽  
Methylation Patterns

Abstract Background We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5′-C-phosphate-G-3′ (CpG) sites from this cohort to predict the progression of diabetic CKD. Methods This cross-sectional study recruited 119 adults. DNA was extracted from blood using the Qiagen QIAampDNA Mini Spin Kit. Genome-wide methylation analysis was performed using Illumina Infinium MethylationEPIC BeadChips (HM850K). Intensity data files were processed and analysed using the minfi and MissMethyl packages for R. We examined the degree of methylation of CpG sites in early versus late diabetic CKD patients for CpG sites with an unadjusted P-value <0.01 and an absolute change in methylation of 5% (n = 239 CpG sites). Results Hierarchical clustering of the 239 CpG sites largely separated the two groups. A heat map for all 239 CpG sites demonstrated distinct methylation patterns in the early versus late groups, with CpG sites showing evidence of progressive change. Based on our differentially methylated region (DMR) analysis of the 239 CpG sites, we highlighted two DMRs, namely the cysteine-rich secretory protein 2 (CRISP2) and piwi-like RNA-mediated gene silencing 1 (PIWIL1) genes. The best predictability for the two groups involved a receiver operating characteristics curve of eight CpG sites alone and achieved an area under the curve of 0.976. Conclusions We have identified distinct DNA methylation patterns between early and late diabetic CKD patients as well as demonstrated novel findings of potential progressive methylation changes across all stages (1–5) of diabetic CKD at specific CpG sites. We have also identified associated genes CRISP2 and PIWIL1, which may have the potential to act as stage-specific diabetes-associated CKD markers, and showed that the use of a panel of eight identified CpG sites alone helps to increase the predictability for the two groups.

Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1807-1817 ◽  
Author(s):  
Jiyoung Lee ◽  
Kimiko Inoue ◽  
Ryuichi Ono ◽  
Narumi Ogonuki ◽  
Takashi Kohda ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genomic Imprinting ◽  
Nuclear Transfer ◽  
Monoallelic Expression ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Male And Female ◽  
Imprinted Gene ◽  
Methylation Patterns

Genomic imprinting is an epigenetic mechanism that causes functional differences between paternal and maternal genomes, and plays an essential role in mammalian development. Stage-specific changes in the DNA methylation patterns of imprinted genes suggest that their imprints are erased some time during the primordial germ cell (PGC) stage, before their gametic patterns are re-established during gametogenesis according to the sex of individuals. To define the exact timing and pattern of the erasure process, we have analyzed parental-origin-specific expression of imprinted genes and DNA methylation patterns of differentially methylated regions (DMRs) in embryos, each derived from a single day 11.5 to day 13.5 PGC by nuclear transfer. Cloned embryos produced from day 12.5 to day 13.5 PGCs showed growth retardation and early embryonic lethality around day 9.5. Imprinted genes lost their parental-origin-specific expression patterns completely and became biallelic or silenced. We confirmed that clones derived from both male and female PGCs gave the same result, demonstrating the existence of a common default state of genomic imprinting to male and female germlines. When we produced clone embryos from day 11.5 PGCs, their development was significantly improved, allowing them to survive until at least the day 11.5 embryonic stage. Interestingly, several intermediate states of genomic imprinting between somatic cell states and the default states were seen in these embryos. Loss of the monoallelic expression of imprinted genes proceeded in a step-wise manner coordinated specifically for each imprinted gene. DNA demethylation of the DMRs of the imprinted genes in exact accordance with the loss of their imprinted monoallelic expression was also observed. Analysis of DNA methylation in day 10.5 to day 12.5 PGCs demonstrated that PGC clones represented the DNA methylation status of donor PGCs well. These findings provide strong evidence that the erasure process of genomic imprinting memory proceeds in the day 10.5 to day 11.5 PGCs, with the timing precisely controlled for each imprinted gene. The nuclear transfer technique enabled us to analyze the imprinting status of each PGC and clearly demonstrated a close relationship between expression and DNA methylation patterns and the ability of imprinted genes to support development.

Sign in / Sign up

Export Citation Format

Share Document