Imprinting by DNA methylation: from transgenes to endogenous gene sequences

Development ◽  
1990 ◽  
Vol 108 (Supplement) ◽  
pp. 99-106 ◽  
Author(s):  
Wolf Reik ◽  
Sarah K. Howlett ◽  
M. Azim Surani
Keyword(s):  
Dna Methylation ◽  
Mouse Genome ◽  
The Other ◽  
Parental Origin ◽  
Specific Interactions ◽  
Gene Sequences ◽  
Reciprocal Crosses ◽  
Endogenous Gene ◽  
Modifier Locus ◽  
Parental Transmission

A number of transgenes in the mouse show variation in methylation and expression phenotypes dependent on parental transmission. It appears that there exist at least two types of transgene imprinting; one is retained on an essentially homozygous background, while the other requires heterozygosity at some modifying loci in the genome and is observed as differences in phenotype in reciprocal crosses. For this type of imprinting to occur, the parental origin of the modifier locus itself is important, and parental asymmetry may involve specific interactions between egg cytoplasm and the chromosomes. Based on the identification of ‘methylation polymorphism’ in the mouse genome, we also show that endogenous gene sequences can undergo imprinting by DNA methylation.

A transgene insertional mutation at an imprinted locus in the mouse genome

Development ◽  
1990 ◽  
Vol 108 (Supplement) ◽  
pp. 73-79
Author(s):  
Julie A. DeLoia ◽  
Davor Solter
Keyword(s):  
Mouse Genome ◽  
Insertion Site ◽  
Parental Origin ◽  
Incomplete Penetrance ◽  
Endogenous Gene ◽  
Functional Differences ◽  
Genetic Imprinting ◽  
Pronuclear Transfer ◽  
Parent Of Origin ◽  
Transgene Insertion

Genetic imprinting in mice results in functional differences in the oocyte and spermatocyte genomes, as evidenced by both genetic and pronuclear transfer experiments. To gain insights into the molecular mechansims involved in the imprinting process, researchers have studied methylation phenotypes and expression of hemizygous transgenes associated with parental origin. In this report, we describe a transgenic mouse lineage in which expression of both the transgene and an endogenous gene at the insertion site are determined by the parent of origin. The mutation caused by transgene insertion shows variable expressivity and incomplete penetrance in addition to a modified dominant pattern of inheritance.

scholarly journals Novobiocin Sensitivity of Salmonella typhimurium dam and/or seqA Mutants

2014 ◽  
Vol 63 (1) ◽  
pp. 51-56 ◽  
Author(s):  
ABDELWAHEB CHATTI ◽  
MERIEM ALOUI ◽  
JIHEN TAGOURTI ◽  
MOUADH MIHOUB ◽  
AHMED LANDOULSI
Keyword(s):  
Dna Methylation ◽  
Stationary Phase ◽  
Salmonella Typhimurium ◽  
The Other ◽  
Protein Profiles ◽  
Wild Type ◽  
Whole Cell ◽  
Expression Levels

This study was carried out to determine the effects of novobiocin, a gyrase inhibitor, on the growth, survival, motility and whole cell proteins of S. Typhimurium dam and/or seqA strains. Our results showed that the dam and seqA/dam mutants are the most sensitive to novobiocin, compared to wild type and seqA strains. Surprisingly, the motility of seqA mutants increased after exposure to novobiocin only in stationary phase cells. All the other strains showed a significant decrease in their motility. The analysis of protein profiles of all strains demonstrated several modifications as manifested by the alteration of the expression levels of certain bands. Our work is therefore of great interest in understanding the effects of novobiocin on S. Typhimurium and the involvement of DNA methylation.

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 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 Universal endogenous gene controls for bisulphite conversion in analysis of plant DNA methylation

Plant Methods ◽  
2011 ◽  
Vol 7 (1) ◽  
pp. 39 ◽  
Author(s):  
Jing Wang ◽  
Chongnan Wang ◽  
Yan Long ◽  
Clare Hopkins ◽  
Smita Kurup ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Endogenous Gene ◽  
Plant Dna

scholarly journals The complexities of ‘otherness’: reflections on embodiment of a young White British woman engaged in cross-generation research involving older people in Indonesia

2014 ◽  
Vol 35 (5) ◽  
pp. 986-1010 ◽  
Author(s):  
MERIEL NORRIS
Keyword(s):  
Older People ◽  
Empirical Research ◽  
The Other ◽  
Specific Interactions ◽  
Potential Influence ◽  
Dynamic Nature ◽  
Mixed Area ◽  
Embodied Experiences ◽  
Active Nature ◽  
Methodological Concern

ABSTRACTIf interviews are to be considered embodied experiences, than the potential influence of the embodied researcher must be explored. A focus on specific attributes such as age or ethnicity belies the complex and negotiated space that both researcher and participant inhabit simultaneously. Drawing on empirical research with stroke survivors in an ethnically mixed area of Indonesia, this paper highlights the importance of considering embodiment as a specific methodological concern. Three specific interactions are described and analysed, illustrating the active nature of the embodied researcher in narrative production and development. The intersectionality of embodied features is evident, alongside their fluctuating influence in time and place. These interactions draw attention to the need to consider the researcher within the interview process and the subsequent analysis and presentation of narrative findings. The paper concludes with a reinforcement of the importance of ongoing and meaningful reflexivity in research, a need to consider the researcher as the other participant, and specifically a call to engage with and present the dynamic nature of embodiment.

Analysis of Additional Virulence Genes and Virulence Gene Regions in Listeria monocytogenes Confirms the Epidemiologic Relevance of Multi-Virulence-Locus Sequence Typing

2008 ◽  
Vol 71 (12) ◽  
pp. 2559-2566 ◽  
Author(s):  
SARA LOMONACO ◽  
YI CHEN ◽  
STEPHEN J. KNABEL
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Listeria Monocytogenes ◽  
Virulence Genes ◽  
Virulence Gene ◽  
The Other ◽  
Evolutionary Divergence ◽  
Gene Sequences ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Molecular Subtyping

Previous molecular subtyping studies have defined four epidemic clones (ECs) of Listeria monocytogenes (ECI, ECII, ECIII, and ECIV). Partial sequences of eight virulence genes were previously shown to be identical within individual ECs of L. monocytogenes. The present study was conducted to determine if the sequences of other virulence genes and virulence gene regions are also conserved within these ECs. Six additional virulence genes—bsh, hly, inlJ, lplA1, pgdA, and srtA—and three additional virulence gene regions of actA, inlA, and inlB were selected based on their role in L. monocytogenes virulence, and intragenic regions of each gene were sequenced. Sequencing was performed on a diverse set of 44 to 48 L. monocytogenes strains. Results demonstrated that the sequenced regions of the nine virulence genes were identical within each of the ECs, and 257 new single nucleotide polymorphism (SNPs) were identified. ECIII (lineage II) was easily distinguishable from the other ECs, as 238 SNPs were observed in ECIII due to its significant evolutionary divergence from lineage I. With regard to the other ECs, there were 5 SNPs that represented an informative set, since these SNPs were able to differentiate specific ECs from all other unrelated strains used in this study. This study confirms our previous finding that virulence gene sequences are highly conserved within individual ECs and contain stable SNPs that can be used to very accurately differentiate ECs of L. monocytogenes from each other and from other diverse strains.

Fruit quality and DNA methylation are affected by parental order in reciprocal crosses of tomato

2020 ◽  
Author(s):  
Magalí Diana Gimenez ◽  
Dana Valeria Vazquez ◽  
Felipe Trepat ◽  
Vladimir Cambiaso ◽  
Gustavo Rubén Rodríguez
Keyword(s):  
Dna Methylation ◽  
Fruit Quality ◽  
Reciprocal Crosses

scholarly journals Copy number variations alter methylation and parallel IGF2 overexpression in adrenal tumors

2015 ◽  
Vol 22 (6) ◽  
pp. 953-967 ◽  
Author(s):  
Helene Myrtue Nielsen ◽  
Alexandre How-Kit ◽  
Carole Guerin ◽  
Frederic Castinetti ◽  
Hans Kristian Moen Vollan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Copy Number ◽  
Methylation Status ◽  
Uniparental Disomy ◽  
Copy Number Variations ◽  
Conclusive Evidence ◽  
Adrenal Tumors ◽  
Benign Tumors ◽  
Parental Origin ◽  
Adrenocortical Carcinomas

Overexpression of insulin growth factor 2 (IGF2) is a hallmark of adrenocortical carcinomas and pheochromocytomas. Previous studies investigating the IGF2/H19 locus have mainly focused on a single molecular level such as genomic alterations or altered DNA methylation levels and the causal changes underlying IGF2 overexpression are still not fully established. In the current study, we analyzed 62 tumors of the adrenal gland from patients with Conn's adenoma (CA, n=12), pheochromocytomas (PCC, n=10), adrenocortical benign tumors (ACBT, n=20), and adrenocortical carcinomas (ACC, n=20). Gene expression, somatic copy number variation of chr11p15.5, and DNA methylation status of three differential methylated regions of the IGF2/H19 locus including the H19 imprinting control region were integratively analyzed. IGF2 overexpression was found in 85% of the ACCs and 100% of the PCCs compared to 23% observed in CAs and ACBTs. Copy number aberrations of chr11p15.5 were abundant in both PCCs and ACCs but while PCCs retained a diploid state, ACCs were frequently tetraploid (7/19). Loss of either a single allele or loss of two alleles of the same parental origin in tetraploid samples resulted in a uniparental disomy-like genotype. These copy number changes correlated with hypermethylation of the H19 ICR suggesting that the lost alleles were the unmethylated maternal alleles. Our data provide conclusive evidence that loss of the maternal allele correlates with IGF2 overexpression in adrenal tumors and that hypermethylation of the H19 ICR is a consequence thereof.

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