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Cell Feb 2019Complex multicellular organisms, such as mammals, express two complete sets of chromosomes per nucleus, combining the genetic material of both parents. However,... (Review)
Review
Complex multicellular organisms, such as mammals, express two complete sets of chromosomes per nucleus, combining the genetic material of both parents. However, epigenetic studies have demonstrated violations to this rule that are necessary for mammalian physiology; the most notable parental allele expression phenomenon is genomic imprinting. With the identification of endogenous imprinted genes, genomic imprinting became well-established as an epigenetic mechanism in which the expression pattern of a parental allele influences phenotypic expression. The expanding study of genomic imprinting is revealing a significant impact on brain functions and associated diseases. Here, we review key milestones in the field of imprinting and discuss mechanisms and systems in which imprinted genes exert a significant role.
Topics: Alleles; Animals; Biological Evolution; Chromosomes; DNA Methylation; Epigenesis, Genetic; Genomic Imprinting; Mammals; Physiological Phenomena
PubMed: 30794780
DOI: 10.1016/j.cell.2019.01.043 -
Cold Spring Harbor Perspectives in... Feb 2014Genomic imprinting affects a subset of genes in mammals and results in a monoallelic, parental-specific expression pattern. Most of these genes are located in clusters... (Review)
Review
Genomic imprinting affects a subset of genes in mammals and results in a monoallelic, parental-specific expression pattern. Most of these genes are located in clusters that are regulated through the use of insulators or long noncoding RNAs (lncRNAs). To distinguish the parental alleles, imprinted genes are epigenetically marked in gametes at imprinting control elements through the use of DNA methylation at the very least. Imprinted gene expression is subsequently conferred through lncRNAs, histone modifications, insulators, and higher-order chromatin structure. Such imprints are maintained after fertilization through these mechanisms despite extensive reprogramming of the mammalian genome. Genomic imprinting is an excellent model for understanding mammalian epigenetic regulation.
Topics: Alleles; Animals; Chromatin; Chromosomes; DNA Methylation; Genomic Imprinting; Histones; Mammals; Parents; RNA, Long Noncoding
PubMed: 24492710
DOI: 10.1101/cshperspect.a018382 -
Heredity Aug 2014
Topics: Animals; Evolution, Molecular; Genomic Imprinting; Humans; Models, Genetic
PubMed: 25026988
DOI: 10.1038/hdy.2014.52 -
Epigenetics Dec 2022Imprinted genes - critical for growth, metabolism, and neuronal function - are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates...
Imprinted genes - critical for growth, metabolism, and neuronal function - are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types. Thus, they are attractive for investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate ICRs in humans by performing whole-genome bisulphite sequencing (WGBS) of DNA derived from the three germ layers and from gametes. We identified 1,488 hemi-methylated candidate ICRs, including 19 of 25 previously characterized ICRs (https://humanicr.org/). Gamete methylation approached 0% or 100% in 332 ICRs (178 paternally and 154 maternally methylated), supporting parent-of-origin-specific methylation, and 65% were in well-described CTCF-binding or DNaseI hypersensitive regions. This draft of the human imprintome will allow for the systematic determination of the role of early-acquired imprinting dysregulation in the pathogenesis of human diseases and developmental and behavioural disorders.
Topics: Adult; Humans; Genomic Imprinting; DNA Methylation; Chromosome Mapping; Alleles; Genomics
PubMed: 35786392
DOI: 10.1080/15592294.2022.2091815 -
PLoS Genetics Aug 2020
Topics: DNA Methylation; Epigenomics; Genomic Imprinting; Humans
PubMed: 32760145
DOI: 10.1371/journal.pgen.1008970 -
Genes & Development Jun 2021Genomic imprinting is the monoallelic expression of a gene based on parent of origin and is a consequence of differential epigenetic marking between the male and female... (Review)
Review
Genomic imprinting is the monoallelic expression of a gene based on parent of origin and is a consequence of differential epigenetic marking between the male and female germlines. Canonically, genomic imprinting is mediated by allelic DNA methylation. However, recently it has been shown that maternal H3K27me3 can result in DNA methylation-independent imprinting, termed "noncanonical imprinting." In this review, we compare and contrast what is currently known about the underlying mechanisms, the role of endogenous retroviral elements, and the conservation of canonical and noncanonical genomic imprinting.
Topics: DNA Methylation; Epigenomics; Genomic Imprinting; Humans; Retroelements
PubMed: 34074696
DOI: 10.1101/gad.348422.121 -
Genes & Development Jan 2020Genomic imprinting is an epigenetic phenomenon leading to parentally biased gene expression. Throughout the years, extensive efforts have been made to characterize the... (Review)
Review
Genomic imprinting is an epigenetic phenomenon leading to parentally biased gene expression. Throughout the years, extensive efforts have been made to characterize the epigenetic marks underlying imprinting in animals and plants. As a result, DNA methylation asymmetries between parental genomes emerged as the primary factor controlling the imprinting status of many genes. Nevertheless, the data accumulated so far suggest that this process cannot solely explain the imprinting of all genes. In this review, we revisit the current models explaining imprinting regulation in plants, and discuss novel regulatory mechanisms that could function independently of parental DNA methylation asymmetries in the establishment of imprinting.
Topics: DNA Methylation; Genomic Imprinting; Models, Genetic; Plants
PubMed: 31896690
DOI: 10.1101/gad.332924.119 -
PLoS Genetics Apr 2020As the maternal-foetal interface, the placenta is essential for the establishment and progression of healthy pregnancy, regulating both foetal growth and maternal... (Review)
Review
As the maternal-foetal interface, the placenta is essential for the establishment and progression of healthy pregnancy, regulating both foetal growth and maternal adaptation to pregnancy. The evolution and functional importance of genomic imprinting are inextricably linked to mammalian placentation. Recent technological advances in mapping and manipulating the epigenome in embryogenesis in mouse models have revealed novel mechanisms regulating genomic imprinting in placental trophoblast, the physiological implications of which are only just beginning to be explored. This review will highlight important recent discoveries and exciting new directions in the study of placental imprinting.
Topics: Animals; DNA Methylation; Female; Genomic Imprinting; Humans; Placenta; Pregnancy; Retroelements
PubMed: 32324732
DOI: 10.1371/journal.pgen.1008709 -
Genes & Development Sep 2023Imprinted gene clusters are confined genomic regions containing genes with parent-of-origin-dependent transcriptional activity. In this issue of , Loftus and colleagues... (Review)
Review
Imprinted gene clusters are confined genomic regions containing genes with parent-of-origin-dependent transcriptional activity. In this issue of , Loftus and colleagues (pp. 829-843) made use of an insightful combination of descriptive approaches, genetic manipulations, and epigenome-editing approaches to show that differences in nuclear topology precede the onset of imprinted expression at the locus. Furthermore, the investigators provide data in line with a model suggesting that parent-of-origin-specific topological differences could be responsible for parent-of-origin-specific enhancer activity and thus imprinted expression.
Topics: Genomic Imprinting; DNA Methylation
PubMed: 37821108
DOI: 10.1101/gad.351216.123 -
Genes Jan 2024Genomic imprinting is a specific mode of gene regulation which particularly accounts for the factors involved in development. Its disturbance affects the fetus, the... (Review)
Review
Genomic imprinting is a specific mode of gene regulation which particularly accounts for the factors involved in development. Its disturbance affects the fetus, the course of pregnancy and even the health of the mother. In children, aberrant imprinting signatures are associated with imprinting disorders (ImpDis). These alterations also affect the function of the placenta, which has consequences for the course of the pregnancy. The molecular causes of ImpDis comprise changes at the DNA level and methylation disturbances (imprinting defects/ImpDefs), and there is an increasing number of reports of both pathogenic fetal and maternal DNA variants causing ImpDefs. These ImpDefs can be inherited, but prediction of the pregnancy complications caused is difficult, as they can cause miscarriages, aneuploidies, health issues for the mother and ImpDis in the child. Due to the complexity of imprinting regulation, each pregnancy or patient with suspected altered genomic imprinting requires a specific workup to identify the precise molecular cause and also careful clinical documentation. This review will cover the current knowledge on the molecular causes of aberrant imprinting signatures and illustrate the need to identify this basis as the prerequisite for personalized genetic and reproductive counselling of families.
Topics: Pregnancy; Female; Child; Humans; Genomic Imprinting; Placenta; Reproductive Techniques, Assisted; Reproduction; DNA
PubMed: 38397153
DOI: 10.3390/genes15020163