scholarly journals Gamete imprinting: setting epigenetic patterns for the next generation

2006 ◽  
Vol 18 (2) ◽  
pp. 63 ◽  
Author(s):  
Jacquetta M. Trasler
Keyword(s):  
Dna Methylation ◽  
Genomic Dna ◽  
Germ Line ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Placental Function ◽  
Early Embryos ◽  
Parent Of Origin ◽  
Methylation Patterns ◽  
Epigenetic Patterns

The acquisition of genomic DNA methylation patterns, including those important for development, begins in the germ line. In particular, imprinted genes are differentially marked in the developing male and female germ cells to ensure parent-of-origin-specific expression in the offspring. Abnormalities in imprints are associated with perturbations in growth, placental function, neurobehavioural processes and carcinogenesis. Based, for the most part, on data from the well-characterised mouse model, the present review will describe recent studies on the timing and mechanisms underlying the acquisition and maintenance of DNA methylation patterns in gametes and early embryos, as well as the consequences of altering these patterns.

scholarly journals Lineage and Parent-of-Origin Effects in DNA Methylation of Honey Bees (Apis mellifera) Revealed by Reciprocal Crosses and Whole-Genome Bisulfite Sequencing

2020 ◽  
Vol 12 (8) ◽  
pp. 1482-1492
Author(s):  
Xin Wu ◽  
David A Galbraith ◽  
Paramita Chatterjee ◽  
Hyeonsoo Jeong ◽  
Christina M Grozinger ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Honey Bees ◽  
Specific Expression ◽  
Africanized Honey Bee ◽  
Allele Specific ◽  
Parent Of Origin ◽  
Origin Effects ◽  
Genetic Background Effects ◽  
Allele Specific Methylation ◽  
Methylation Patterns

Abstract Parent-of-origin methylation arises when the methylation patterns of a particular allele are dependent on the parent it was inherited from. Previous work in honey bees has shown evidence of parent-of-origin-specific expression, yet the mechanisms regulating such pattern remain unknown in honey bees. In mammals and plants, DNA methylation is known to regulate parent-of-origin effects such as genomic imprinting. Here, we utilize genotyping of reciprocal European and Africanized honey bee crosses to study genome-wide allele-specific methylation patterns in sterile and reproductive individuals. Our data confirm the presence of allele-specific methylation in honey bees in lineage-specific contexts but also importantly, though to a lesser degree, parent-of-origin contexts. We show that the majority of allele-specific methylation occurs due to lineage rather than parent-of-origin factors, regardless of the reproductive state. Interestingly, genes affected by allele-specific DNA methylation often exhibit both lineage and parent-of-origin effects, indicating that they are particularly labile in terms of DNA methylation patterns. Additionally, we re-analyzed our previous study on parent-of-origin-specific expression in honey bees and found little association with parent-of-origin-specific methylation. These results indicate strong genetic background effects on allelic DNA methylation and suggest that although parent-of-origin effects are manifested in both DNA methylation and gene expression, they are not directly associated with each other.

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.

scholarly journals Bumblebee worker castes show differences in allele-specific DNA methylation and allele-specific expression

2020 ◽  
Author(s):  
H. Marshall ◽  
A.R.C. Jones ◽  
Z.N. Lonsdale ◽  
E.B. Mallon
Keyword(s):  
Dna Methylation ◽  
Bombus Terrestris ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Genome Wide ◽  
Expression Bias ◽  
Allele Specific ◽  
Parent Of Origin ◽  
Worker Castes

AbstractAllele-specific expression is when one allele of a gene shows higher levels of expression compared to the other allele, in a diploid organism. Genomic imprinting is an extreme example of this, where some genes exhibit allele-specific expression in a parent-of-origin manner. Recent work has identified potentially imprinted genes in species of Hymenoptera. However, the molecular mechanism which drives this allelic expression bias remains unknown. In mammals DNA methylation is often associated with imprinted genes. DNA methylation systems have been described in species of Hymenoptera, providing a candidate imprinting mechanism. Using previously generated RNA-Seq and whole genome bisulfite sequencing from reproductive and sterile bumblebee (Bombus terrestris) workers we have identified genome-wide allele-specific expression and allele-specific DNA methylation. The majority of genes displaying allele-specific expression are common between reproductive castes and the proportion of allele-specific expression bias generally varies between colonies. We have also identified genome-wide allele-specific DNA methylation patterns in both castes. There is no significant overlap between genes showing allele-specific expression and allele-specific methylation. These results indicate that DNA methylation does not directly drive genome-wide allele-specific expression in this species. Only a small number of the genes identified may be ‘imprinted’ and it may be these genes which are associated with allele-specific DNA methylation. Future work utilising reciprocal crosses to identify parent-of-origin DNA methylation will further clarify the role of DNA methylation in parent-of-origin allele-specific expression.

scholarly journals Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting

2021 ◽  
Vol 118 (29) ◽  
pp. e2104445118
Author(s):  
Jessica A. Rodrigues ◽  
Ping-Hung Hsieh ◽  
Deling Ruan ◽  
Toshiro Nishimura ◽  
Manoj K. Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Genomic Imprinting ◽  
Small Rnas ◽  
Imprinted Genes ◽  
Dna Hypomethylation ◽  
Transcription Start ◽  
Specific Expression ◽  
Parent Of Origin

Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution.

scholarly journals Timing and Sequence Requirements Defined for Embryonic Maintenance of Imprinted DNA Methylation at Rasgrf1

2006 ◽  
Vol 26 (24) ◽  
pp. 9564-9570 ◽  
Author(s):  
Rebecca Holmes ◽  
Yanjie Chang ◽  
Paul D. Soloway
Keyword(s):  
Dna Methylation ◽  
Germ Line ◽  
Direct Repeat ◽  
Repeat Sequence ◽  
Paternal Allele ◽  
Imprinted Genes ◽  
Male Germ Line ◽  
Specific Expression ◽  
Morula Stage ◽  
Allele Specific

ABSTRACT Epigenetic programming is critical for normal development of mammalian embryos. Errors cause misexpression of genes and aberrant development (E. Li, C. Beard, and R. Jaenisch, Nature 366:362-365, 1993). Imprinted genes are important targets of epigenetic regulation, but little is known about how the epigenetic patterns are established in the parental germ lines and maintained in the embryo. Paternal allele-specific expression at the imprinted Rasgrf1 locus in mice is controlled by paternal allele-specific methylation at a differentially methylated domain (DMD). DMD methylation is in turn controlled by a direct repeat sequence immediately downstream of the DMD which is required for establishing Rasgrf1 methylation in the male germ line (B. J. Yoon et al., Nat. Genet. 30:92-96, 2002). To determine if these repeats have a role in methylation maintenance, we developed a conditional deletion of the repeat sequence in mice and showed that the repeats are also required during a narrow interval to maintain paternal methylation of Rasgrf1 in developing embryos. Removing the repeats upon fertilization caused a total loss of methylation by the morula stage, but by the epiblast stage, the repeats were completely dispensable for methylation maintenance. This developmental interval coincides with genome-wide demethylation and remethylation in mice which most imprinted genes resist. Our data show that the Rasgrf1 repeats serve at least two functions: first, to establish Rasgrf1 DNA methylation in the male germ line, and second, to resist global demethylation in the preimplantation embryo.

scholarly journals Parent of origin gene expression in a founder population identifies two new imprinted genes at known imprinted regions

2018 ◽  
Author(s):  
Sahar V. Mozaffari ◽  
Michelle M. Stein ◽  
Kevin M. Magnaye ◽  
Dan L. Nicolae ◽  
Carole Ober
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Expression Data ◽  
Imprinted Genes ◽  
Genotype Data ◽  
Expression Data ◽  
Rna Seq ◽  
Specific Expression ◽  
Allele Specific ◽  
Parent Of Origin

AbstractGenomic imprinting is the phenomena that leads to silencing of one copy of a gene inherited from a specific parent. Mutations in imprinted regions have been involved in diseases showing parent of origin effects. Identifying genes with evidence of parent of origin expression patterns in family studies allows the detection of more subtle imprinting. Here, we use allele specific expression in lymphoblastoid cell lines from 306 Hutterites related in a single pedigree to provide formal evidence for parent of origin effects. We take advantage of phased genotype data to assign parent of origin to RNA-seq reads in individuals with gene expression data. Our approach identified known imprinted genes, two putative novel imprinted genes, and 14 genes with asymmetrical parent of origin gene expression. We used gene expression in peripheral blood leukocytes (PBL) to validate our findings, and then confirmed imprinting control regions (ICRs) using DNA methylation levels in the PBLs.Author SummaryLarge scale gene expression studies have identified known and novel imprinted genes through allele specific expression without knowing the parental origins of each allele. Here, we take advantage of phased genotype data to assign parent of origin to RNA-seq reads in 306 individuals with gene expression data. We identified known imprinted genes as well as two novel imprinted genes in lymphoblastoid cell line gene expression. We used gene expression in PBLs to validate our findings, and DNA methylation levels in PBLs to confirm previously characterized imprinting control regions that could regulate these imprinted genes.

scholarly journals Novel imprints in mouse blastocysts are predominantly DNA methylation independent

2020 ◽  
Author(s):  
Laura Santini ◽  
Florian Halbritter ◽  
Fabian Titz-Teixeira ◽  
Toru Suzuki ◽  
Maki Asami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genomic Dna ◽  
Bisulfite Sequencing ◽  
Preimplantation Embryos ◽  
Imprinted Genes ◽  
Whole Genome ◽  
Specific Expression ◽  
Complex Program ◽  
Genome Bisulfite Sequencing ◽  
Parent Of Origin

ABSTRACTIn mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation.

scholarly journals Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Laura Santini ◽  
Florian Halbritter ◽  
Fabian Titz-Teixeira ◽  
Toru Suzuki ◽  
Maki Asami ◽  
...  
Keyword(s):  
Bisulfite Sequencing ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Imprinted Genes ◽  
Specific Expression ◽  
Histone 3 ◽  
Complex Program ◽  
Genome Bisulfite Sequencing ◽  
Mammalian Genomes ◽  
Parent Of Origin

AbstractIn mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.

scholarly journals ZFP57 dictates allelic expression switch of target imprinted genes

2021 ◽  
Vol 118 (5) ◽  
pp. e2005377118
Author(s):  
Weijun Jiang ◽  
Jiajia Shi ◽  
Jingjie Zhao ◽  
Qiu Wang ◽  
Dan Cong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Notch Signaling ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mouse Embryos ◽  
The Other ◽  
Allelic Expression ◽  
Monoallelic Expression ◽  
Imprinted Genes ◽  
Parent Of Origin

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin–dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.

scholarly journals DNA Methylation Patterns in Saliva of Tobacco users with High-Risk Oral Potentially Malignant Disorders

2021 ◽  
pp. 129-137
Author(s):  
Mimansha Patel ◽  
Madhuri Nitin Gawande ◽  
Minal Shashikant Chaudhary ◽  
Alka Harish Hande
Keyword(s):  
Dna Methylation ◽  
High Risk ◽  
Malignant Transformation ◽  
Promoter Methylation ◽  
Genomic Dna ◽  
Premalignant Lesions ◽  
Oral Potentially Malignant Disorders ◽  
Potentially Malignant Disorders ◽  
Potentially Malignant ◽  
Methylation Patterns

Background: “Oral Potentially Malignant Disorder (OPMD)” is a well-known symptom that, if untreated, can be carcinogenic. It includes leukoplakia, erythroplakia or erythroleukoplakia. One of the typical premalignant lesions of the oral cavity is “oral leukoplakias (OLs),” which frequently precedes “OSCCs.”OLs with dysplastic characteristics are considered to be at a higher risk of “malignant transformation.” So, early diagnosis of "oral squamous cell carcinomas (OSCCs)" is desperately required to enhance patient prognosis and quality of life (QOL).As a result, we examined the distinctive promoter methylation presence in high-risk OLs. Objectives: To detect, compare & correlate “DNA methylation” patterns in normal individuals, tobacco users without disease and tobacco users with the disease. Methodology: With the participants' full consent, 48 saliva samples were obtained and prepared. DNA isolation, restriction digestion of genomic DNA, extraction of restriction enzyme digested genomic DNA, Polymerase Chain Reaction (PCR), and Agarose Gel Electrophoresis (AGE) were all carried out. Expected results: This study will help us to assess the use of Saliva as an aid to identifying both high and low risk “Oral Potentially Malignant Disorders.” Conclusion: Peculiar promoter methylation of various genes was related to a high possibility of malignant transformation in OLs.

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