scholarly journals Parental imprinting studied by allele-specific primer extension after PCR: paternal X chromosome-linked genes are transcribed prior to preferential paternal X chromosome inactivation.

1992 ◽  
Vol 89 (21) ◽  
pp. 10469-10473 ◽  
Author(s):  
J. Singer-Sam ◽  
V. Chapman ◽  
J. M. LeBon ◽  
A. D. Riggs
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Primer Extension ◽  
Chromosome Inactivation ◽  
Specific Primer ◽  
Parental Imprinting ◽  
Allele Specific

scholarly journals Mouse endogenous X-linked genes do not show lineage-specific delayed inactivation during development

1995 ◽  
Vol 65 (3) ◽  
pp. 223-227 ◽  
Author(s):  
Jeanne M. Lebon ◽  
Patrick P. L. Tam ◽  
Judith Singer-Sam ◽  
Arthur D. Riggs ◽  
Seong-Seng Tan
Keyword(s):  
X Chromosome ◽  
Female Mouse ◽  
X Chromosome Inactivation ◽  
Mouse Embryos ◽  
Primer Extension ◽  
Rt Pcr ◽  
Single Nucleotide ◽  
Allele Specific ◽  
Endogenous Genes ◽  
Single Nucleotide Primer Extension

SummaryX chromosome inactivation (XCI) has been assumed to be complete in all cells of female mouse embryos at about 6 d post coitum (dpc). However, a recent study on β-galactosidase expression of an X-linkedlacZtransgene suggests that XCI is probably not complete several days after this time in some lineages. To help resolve this issue, we analysed XCI in embryos which carry the T(X;16)16H (Searle's) translocation and are heterozygous at the X-linkedHprtandPgk-1genes. The quantitative RT-PCR single nucleotide primer extension (SNuPE) assay was used to measureHprtandPgk-1allele-specific transcripts in embryos 9·5 dpc. No transcripts from the normal X chromosome were found in any of the tissues tested, indicating that inactivation was complete for these endogenous genes.

scholarly journals DAMEfinder: A method to detect differential allele-specific methylation

2019 ◽  
Author(s):  
Stephany Orjuela ◽  
Dania Machlab ◽  
Mirco Menigatti ◽  
Giancarlo Marra ◽  
Mark D. Robinson
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
X Chromosome ◽  
Regulation Of Gene Expression ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Cancer Dataset ◽  
Cpg Sites ◽  
Allele Specific ◽  
Allele Specific Methylation

AbstractDNA methylation is a highly studied epigenetic signature that is associated with regulation of gene expression, whereby genes with high levels of promoter methylation are generally repressed. Genomic imprinting occurs when one of the parental alleles is methylated, i.e, when there is inherited allele-specific methylation (ASM). A special case of imprinting occurs during X chromosome inactivation in females, where one of the two X chromosomes is silenced, in order to achieve dosage compensation between the sexes. Another more widespread form of ASM is sequence dependent (SD-ASM), where ASM is linked to a nearby heterozygous single nucleotide polymorphism (SNP).We developed a method to screen for genomic regions that exhibit loss or gain of ASM in samples from two conditions (treatments, diseases, etc.). The method relies on the availability of bisulfite sequencing data from multiple samples of the two conditions. We leverage other established computational methods to screen for these regions within a new R package called DAMEfinder. It calculates an ASM score for all CpG sites or pairs in the genome of each sample, and then quantifies the change in ASM between conditions. It then clusters nearby CpG sites with consistent change into regions.In the absence of SNP information, our method relies only on reads to quantify ASM. This novel ASM score compares favourably to current methods that also screen for ASM. Not only does it easily discern between imprinted and non-imprinted regions, but also females from males based on X chromosome inactivation. We also applied DAMEfinder to a colorectal cancer dataset and observed that colorectal cancer subtypes are distinguishable according to their ASM signature. We also re-discover known cases of loss of imprinting.We have designed DAMEfinder to detect regions of differential ASM (DAMEs), which is a more refined definition of differential methylation, and can therefore help in breaking down the complexity of DNA methylation and its influence in development and disease.

scholarly journals Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming

2019 ◽  
Author(s):  
Adrian Janiszewski ◽  
Irene Talon ◽  
Juan Song ◽  
Natalie De Geest ◽  
San Kit To ◽  
...  
Keyword(s):  
Gene Silencing ◽  
X Chromosome ◽  
Transcriptional Activation ◽  
Histone Deacetylases ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Early Genes ◽  
Chromatin Regulators ◽  
Allele Specific ◽  
Induced Pluripotent

ABSTRACTBackgroundInduction and reversal of chromatin silencing is critical for successful development, tissue homeostasis and the derivation of induced pluripotent stem cells (iPSCs). X-chromosome inactivation (XCI) and reactivation (XCR) in female cells represent chromosome-wide transitions between active and inactive chromatin states. While XCI has long been studied and provided important insights into gene regulation, the dynamics and mechanisms underlying the reversal of stable chromatin silencing of X-linked genes are much less understood. Here, we use allele-specific transcriptomic approaches to study XCR during mouse iPSC reprogramming in order to elucidate the timing and mechanisms of chromosome-wide reversal of gene silencing.ResultsWe show that XCR is hierarchical, with subsets of genes reactivating early, late and very late. Early genes are activated before the onset of late pluripotency genes activation and the complete silencing of the long non-coding RNA (lncRNA) Xist. These genes are located genomically closer to genes that escape XCI, unlike those reactivating late. Interestingly, early genes also show increased pluripotency transcription factor (TF) binding. We also reveal that histone deacetylases (HDACs) restrict XCR in reprogramming intermediates and that the severe hypoacetylation state of the Xi persists until late reprogramming stages.ConclusionsAltogether, these results reveal the timing of transcriptional activation of mono-allelically repressed genes during iPSC reprogramming, and suggest that allelic activation involves the combined action of chromatin topology, pluripotency transcription factors and chromatin regulators. These findings are important for our understanding of gene silencing, maintenance of cell identity, reprogramming and disease.

scholarly journals Diverse mechanisms for epigenetic imprinting in mammals

2021 ◽  
Author(s):  
Daniel Andergassen ◽  
Zachary D Smith ◽  
John L Rinn ◽  
Alexander Meissner
Keyword(s):  
Genomic Imprinting ◽  
X Chromosome ◽  
Gene Clusters ◽  
Endogenous Retrovirus ◽  
X Chromosome Inactivation ◽  
Polycomb Group ◽  
Chromosome Inactivation ◽  
Epigenetic Mechanisms ◽  
Specific Expression ◽  
Allele Specific

Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to direct allele-specific expression. Despite their critical roles in embryonic development, how universal epigenetic regulators coordinate these specific tasks from single locus to chromosome-scale remains understudied. Here, we systematically disrupted multiple essential epigenetic pathways within polymorphic F1 zygotes to examine postimplantation effects on canonical and non-canonical genomic imprinting as well as X chromosome inactivation. We find that DNA methylation and Polycomb group repressors are both indispensable for autosomal imprinting, albeit at distinct gene sets. Moreover, the extraembryonic ectoderm relies on a broader spectrum of unique imprinting mechanisms, including non-canonical targeting of maternal endogenous retrovirus (ERV) driven promoters by G9a. We further utilize our data to identify Polycomb dependent and independent gene clusters on the imprinted X chromosome, which appears to reflect distinct domains of Xist-mediated suppression. Our data has allowed us to assemble a comprehensive inventory of the epigenetic mechanisms utilized in eutherian mammals to maintain parent-specific imprinting, including an expanded view of the placental lineage that comprises multiple unique pathways.

X-linked CNV and skewed X-chromosome inactivation

2020 ◽  
pp. 19-21
Author(s):  
Е.А. Фонова ◽  
Е.Н. Толмачева ◽  
А.А. Кашеварова ◽  
М.Е. Лопаткина ◽  
К.А. Павлова ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intellectual Disability ◽  
X Chromosome ◽  
Copy Number ◽  
Copy Number Variations ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome X ◽  
Skewed X Chromosome Inactivation

Смещение инактивации Х-хромосомы может быть следствием и маркером нарушения клеточной пролиферации при вариациях числа копий ДНК на Х-хромосоме. Х-сцепленные CNV выявляются как у женщин с невынашиванием беременности и смещением инактивации Х-хромосомы (с частотой 33,3%), так и у пациентов с умственной отсталостью и смещением инактивацией у их матерей (с частотой 40%). A skewed X-chromosome inactivation can be a consequence and a marker of impaired cell proliferation in the presence of copy number variations (CNV) on the X chromosome. X-linked CNVs are detected in women with miscarriages and a skewed X-chromosome inactivation (with a frequency of 33.3%), as well as in patients with intellectual disability and skewed X-chromosome inactivation in their mothers (with a frequency of 40%).

scholarly journals X-Linked Emery–Dreifuss Muscular Dystrophy: Study Of X-Chromosome Inactivation and Its Relation with Clinical Phenotypes in Female Carriers

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 919 ◽  
Author(s):  
Viggiano ◽  
Madej-Pilarczyk ◽  
Carboni ◽  
Picillo ◽  
Ergoli ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
X Chromosome ◽  
Clinical Symptoms ◽  
Fibrous Tissue ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Cardiac Conduction ◽  
Asymptomatic Carriers ◽  
Cardiac Symptoms ◽  
Female Carriers

X-linked Emery–Dreifuss muscular dystrophy (EDMD1) affects approximately 1:100,000 male births. Female carriers are usually asymptomatic but, in some cases, they may present clinical symptoms after age 50 at cardiac level, especially in the form of conduction tissue anomalies. The aim of this study was to evaluate the relation between heart involvement in symptomatic EDMD1 carriers and the X-chromosome inactivation (XCI) pattern. The XCI pattern was determined on the lymphocytes of 30 symptomatic and asymptomatic EDMD1 female carriers—25 familial and 5 sporadic cases—seeking genetic advice using the androgen receptor (AR) methylation-based assay. Carriers were subdivided according to whether they were above or below 50 years of age. A variance analysis was performed to compare the XCI pattern between symptomatic and asymptomatic carriers. The results show that 20% of EDMD1 carriers had cardiac symptoms, and that 50% of these were ≥50 years of age. The XCI pattern was similar in both symptomatic and asymptomatic carriers. Conclusions: Arrhythmias in EDMD1 carriers poorly correlate on lymphocytes to a skewed XCI, probably due to (a) the different embryological origin of cardiac conduction tissue compared to lymphocytes or (b) the preferential loss of atrial cells replaced by fibrous tissue.

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