Upregulation of imprinted genes in mice: An insight into the intensity of gene expression and the evolution of genomic imprinting

Genomic imprinting is a form of non-Mendelian epigenetic inheritance that is defined by differential gene expression depending on its parental origin — maternal or paternal. It is known about 60 imprinted genes many of which effect significantly on the fetus growth and development. Methylation of DNA cytosine bases that defines the interaction of DNA and proteins identifying the modified bases and controls the gene expression through chromatin compacting-decompacting mechanism, is a main epigenetic genom modifier. Disturbances in monoallelic gene expression lead to the development of a special class of human hereditary diseases — genomic imprinting diseases.

Download Full-text

Epigenetic signatures associated with imprinted paternally-expressed genes in the Arabidopsis endosperm

10.1101/423137 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jordi Moreno-Romero ◽

Gerardo Del Toro-De León ◽

Vikash Kumar Yadav ◽

Juan Santos-González ◽

Claudia Köhler

Keyword(s):

Gene Expression ◽

Genomic Imprinting ◽

High Accuracy ◽

Preimplantation Embryos ◽

Specific Gene ◽

Imprinted Genes ◽

Specific Gene Expression ◽

Vegetative Tissues ◽

Functional Relevance ◽

Epigenetic Signatures

ABSTRACTBackgroundImprinted genes are epigenetically modified during gametogenesis and maintain the established epigenetic signatures after fertilization, causing parental-specific gene expression.ResultsIn this study, we show that imprinted paternally-expressed genes (PEGs) in the Arabidopsis endosperm are marked by an epigenetic signature of Polycomb Repressive Complex2 (PRC2)-mediated H3K27me3 together with heterochromatic H3K9me2 and CHG methylation, which specifically mark the silenced maternal alleles of PEGs. The co-occurrence of H3K27me3 and H3K9me2 on defined loci in the endosperm drastically differs from the strict separation of both pathways in vegetative tissues, revealing tissue-specific employment of repressive epigenetic pathways in plants. Based on the presence of this epigenetic signature on maternal alleles we were able to predict known PEGs at high accuracy and identified several new PEGs that we confirmed using INTACT-based transcriptomes generated in this study.ConclusionsThe presence of the three repressive epigenetic marks, H3K27me3, H3K9me2, and CHG methylation on the maternal alleles in the endosperm serves as a specific epigenetic signature that allows to predict genes with parental-specific gene expression. Our study reveals that there are substantially more PEGs than previously identified, indicating that paternal-specific gene expression is of higher functional relevance than currently estimated. The combined activity of PRC2-mediated H3K27me3 together with the heterochromatic H3K9me3 has also been reported to silence the maternal Xist locus in mammalian preimplantation embryos, suggesting convergent employment of both pathways during the evolution of genomic imprinting.

Download Full-text

Genomic imprinting and human disease

Essays in Biochemistry ◽

10.1042/bse0480187 ◽

2010 ◽

Vol 48 ◽

pp. 187-200 ◽

Cited By ~ 73

Author(s):

Ryutaro Hirasawa ◽

Robert Feil

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Genomic Imprinting ◽

Developmental Disorders ◽

Molecular Mechanisms ◽

Germ Line ◽

Imprinted Genes ◽

Foetal Growth ◽

Sequence Elements ◽

Covalent Modifications

In many epigenetic phenomena, covalent modifications on DNA and chromatin mediate somatically heritable patterns of gene expression. Genomic imprinting is a classical example of epigenetic regulation in mammals. To date, more than 100 imprinted genes have been identified in humans and mice. Many of these are involved in foetal growth and deve lopment, others control behaviour. Mono-allelic expression of imprinted genes depends on whether the gene is inherited from the mother or the father. This remarkable pattern of expression is controlled by specialized sequence elements called ICRs (imprinting control regions). ICRs are marked by DNA methylation on one of the two parental alleles. These allelic marks originate from either the maternal or the paternal germ line. Perturbation of the allelic DNA methylation at ICRs is causally involved in several human diseases, including the Beckwith–Wiedemann and Silver–Russell syndromes, associated with aberrant foetal growth. Perturbed imprinted gene expression is also implicated in the neuro-developmental disorders Prader–Willi syndrome and Angelman syndrome. Embryo culture and human-assisted reproduction procedures can increase the occurrence of imprinting-related disorders. Recent research shows that, besides DNA methylation, covalent histone modifications and non-histone proteins also contribute to imprinting regulation. The involvement of imprinting in specific human pathologies (and in cancer) emphasizes the need to further explore the underlying molecular mechanisms.

Download Full-text

Associations between imprinted gene expression in the placenta, human fetal growth and preeclampsia

Biology Letters ◽

10.1098/rsbl.2017.0643 ◽

2017 ◽

Vol 13 (11) ◽

pp. 20170643 ◽

Cited By ~ 8

Author(s):

Julian K. Christians ◽

Katherine Leavey ◽

Brian J. Cox

Keyword(s):

Gene Expression ◽

Genomic Imprinting ◽

Fetal Growth ◽

Placental Insufficiency ◽

Imprinted Genes ◽

Nutrient Allocation ◽

Imprinted Gene ◽

Expression Levels ◽

Kinship Theory ◽

Coordinated Regulation

Genomic imprinting is essential for normal placental and fetal growth. One theory to explain the evolution of imprinting is the kinship theory (KT), which predicts that genes that are paternally expressed will promote fetal growth, whereas maternally expressed genes will suppress growth. We investigated the expression of imprinted genes using microarray measurements of expression in term placentae. Correlations between birthweight and the expression levels of imprinted genes were more significant than for non-imprinted genes, but did not tend to be positive for paternally expressed genes and negative for maternally expressed genes. Imprinted genes were more dysregulated in preeclampsia (a disorder associated with placental insufficiency) than randomly selected genes, and we observed an excess of patterns of dysregulation in preeclampsia that would be expected to reduce nutrient allocation to the fetus, given the predictions of the KT. However, we found no evidence of coordinated regulation among these imprinted genes. A few imprinted genes have previously been shown to be associated with fetal growth and preeclampsia, and our results indicate that this is true for a broader set of imprinted genes.

Download Full-text

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104445118 ◽

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.

Download Full-text

Molecular mechanisms of genomic imprinting and clinical implications for cancer

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399410001717 ◽

2011 ◽

Vol 13 ◽

Cited By ~ 53

Author(s):

Santiago Uribe-Lewis ◽

Kathryn Woodfine ◽

Lovorka Stojic ◽

Adele Murrell

Keyword(s):

Gene Expression ◽

Genomic Imprinting ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Early Event ◽

Imprinted Genes ◽

Epigenetic Changes ◽

Imprinted Gene ◽

Growth Loss

Genomic imprinting is an epigenetic marking of genes in the parental germline that ensures the stable transmission of monoallelic gene expression patterns in a parent-of-origin-specific manner. Epigenetic marking systems are thus able to regulate gene activity independently of the underlying DNA sequence. Several imprinted gene products regulate cell proliferation and fetal growth; loss of their imprinted state, which effectively alters their dosage, might promote or suppress tumourigenic processes. Conversely, global epigenetic changes that underlie tumourigenesis might affect imprinted gene expression. Here, we review imprinted genes with regard to their roles in epigenetic predisposition to cancer, and discuss acquired epigenetic changes (DNA methylation, histone modifications and chromatin conformation) either as a result of cancer or as an early event in neoplasia. We also address recent work showing the potential role of noncoding RNA in modifying chromatin and affecting imprinted gene expression, and summarise the effects of loss of imprinting in cancer with regard to the roles that imprinted genes play in regulating growth signalling cascades. Finally, we speculate on the clinical applications of epigenetic drugs in cancer.

Download Full-text

Faculty Opinions recommendation of Detection of Imprinted Genes by Single-Cell Allele-Specific Gene Expression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727301661.793529626 ◽

2017 ◽

Author(s):

Hans van Bokhoven

Keyword(s):

Gene Expression ◽

Single Cell ◽

Specific Gene ◽

Imprinted Genes ◽

Specific Gene Expression ◽

Allele Specific

Download Full-text

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

Current Medicinal Chemistry ◽

10.2174/0929867325666181112090648 ◽

2020 ◽

Vol 27 (20) ◽

pp. 3330-3345

Author(s):

Ana G. Rodríguez-Hernández ◽

Rafael Vazquez-Duhalt ◽

Alejandro Huerta-Saquero

Keyword(s):

Gene Expression ◽

Immune Responses ◽

Cellular Response ◽

Cellular Level ◽

Membrane Interactions ◽

Daily Lives ◽

Cellular Physiology ◽

Associated Proteins ◽

First Contact ◽

Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

Download Full-text

Gene Expression and Carcass Traits Are Different between Different Quality Grade Groups in Red-Faced Hereford Steers

Animals ◽

10.3390/ani11071910 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1910

Author(s):

Bailey Engle ◽

Molly Masters ◽

Jane Ann Boles ◽

Jennifer Thomson

Keyword(s):

Gene Expression ◽

Transcriptome Profiling ◽

Fat Deposition ◽

Lower Shear ◽

The Us ◽

Quality Grade ◽

Longissimus Lumborum ◽

Muscle Biochemistry ◽

Marbling Deposition ◽

Insight Into

Fat deposition is important to carcass value and some palatability characteristics. Carcasses with higher USDA quality grades produce more value for producers and processors in the US system and are more likely to have greater eating satisfaction. Using genomics to identify genes impacting marbling deposition provides insight into muscle biochemistry that may lead to ways to better predict fat deposition, especially marbling and thus quality grade. Hereford steers (16) were managed the same from birth through harvest after 270 days on feed. Samples were obtained for tenderness and transcriptome profiling. As expected, steaks from Choice carcasses had a lower shear force value than steaks from Select carcasses; however, steaks from Standard carcasses were not different from steaks from Choice carcasses. A significant number of differentially expressed (DE) genes was observed in the longissimus lumborum between Choice and Standard carcass RNA pools (1257 genes, p < 0.05), but not many DE genes were observed between Choice and Select RNA pools. Exploratory analysis of global muscle tissue transcriptome from Standard and Choice carcasses provided insight into muscle biochemistry, specifically the upregulation of extracellular matrix development and focal adhesion pathways and the downregulation of RNA processing and metabolism in Choice versus Standard. Additional research is needed to explore the function and timing of gene expression changes.

Download Full-text