Relevance of genomic imprinting in intrauterine human growth expression of CDKN1C, H19, IGF2, KCNQ1 and PHLDA2 imprinted genes

The cis-acting regulatory sequences of imprinted gene loci, called imprinting control regions (ICRs), acquire specific imprint marks in germ cells, including DNA methylation. These epigenetic imprints ensure that imprinted genes are expressed exclusively from either the paternal or the maternal allele in offspring. The last few years have witnessed a rapid increase in studies on how and when ICRs become marked by and subsequently maintain such epigenetic modifications. These novel findings are summarised in this review, which focuses on the germline acquisition of DNA methylation imprints and particularly on the combined role of primary sequence specificity, chromatin configuration, non-histone proteins and transcriptional events.

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Genomic Imprinting of Dopa decarboxylase in Heart and Reciprocal Allelic Expression with Neighboring Grb10

Molecular and Cellular Biology ◽

10.1128/mcb.00862-07 ◽

2007 ◽

Vol 28 (1) ◽

pp. 386-396 ◽

Cited By ~ 28

Author(s):

Trevelyan R. Menheniott ◽

Kathryn Woodfine ◽

Reiner Schulz ◽

Andrew J. Wood ◽

David Monk ◽

...

Keyword(s):

Genomic Imprinting ◽

Promoter Region ◽

Germ Line ◽

Differential Methylation ◽

Dopa Decarboxylase ◽

Imprinted Genes ◽

Chromosome 11 ◽

Imprinted Gene ◽

Line Methylation ◽

Intron 1

ABSTRACT By combining a tissue-specific microarray screen with mouse uniparental duplications, we have identified a novel imprinted gene, Dopa decarboxylase (Ddc), on chromosome 11. Ddc_exon1a is a 2-kb transcript variant that initiates from an alternative first exon in intron 1 of the canonical Ddc transcript and is paternally expressed in trabecular cardiomyocytes of the embryonic and neonatal heart. Ddc displays tight conserved linkage with the maternally expressed and methylated Grb10 gene, suggesting that these reciprocally imprinted genes may be coordinately regulated. In Dnmt3L mutant embryos that lack maternal germ line methylation imprints, we show that Ddc is overexpressed and Grb10 is silenced. Their imprinting is therefore dependent on maternal germ line methylation, but the mechanism at Ddc does not appear to involve differential methylation of the Ddc_exon1a promoter region and may instead be provided by the oocyte mark at Grb10. Our analysis of Ddc redefines the imprinted Grb10 domain on mouse proximal chromosome 11 and identifies Ddc_exon1a as the first example of a heart-specific imprinted gene.

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Genomic imprinting and its role in ethiology of human hereditary diseases

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2004-3-8-17 ◽

2004 ◽

Vol 3 (3) ◽

pp. 8-17

Author(s):

S. A. Nazarenko

Keyword(s):

Gene Expression ◽

Genomic Imprinting ◽

Special Class ◽

Growth And Development ◽

Epigenetic Inheritance ◽

Hereditary Diseases ◽

Parental Origin ◽

Imprinted Genes ◽

Methylation Of Dna ◽

Differential Gene

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.

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Contribution of Placental Genomic Imprinting and Identification of Imprinted Genes

The Guide to Investigation of Mouse Pregnancy ◽

10.1016/b978-0-12-394445-0.00023-0 ◽

2014 ◽

pp. 275-284 ◽

Cited By ~ 1

Author(s):

Laura C. Kusinski ◽

Wendy N. Cooper ◽

Ionel Sandovici ◽

Miguel Constância

Keyword(s):

Genomic Imprinting ◽

Imprinted Genes

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Imprinting analysis in the Acrodysplasia region of mouse chromosome 12

Bioscience Reports ◽

10.1042/bsr20090009 ◽

2009 ◽

Vol 30 (2) ◽

pp. 119-124 ◽

Cited By ~ 1

Author(s):

Erin N. McMurray ◽

Eric D. Rogers ◽

Jennifer V. Schmidt

Keyword(s):

Mouse Chromosome ◽

Genomic Imprinting ◽

Critical Region ◽

The Other ◽

Chromosome 12 ◽

Imprinted Genes ◽

Skeletal Abnormalities ◽

Mouse Mutation ◽

Parent Of Origin

The insertional mouse mutation Adp (Acrodysplasia) confers a parent-of-origin developmental phenotype, with animals inheriting the mutation from their father showing skeletal abnormalities, whereas those inheriting the mutation from their mother are normal. This parental-specific phenotype, along with mapping of the insertion to a region of chromosome 12 proposed to contain imprinted genes, suggested that disruption of genomic imprinting might underlie the Adp phenotype. Genomic imprinting is the process by which autosomal genes are epigenetically silenced on one of the two parental alleles; imprinting mutation phenotypes manifest after inheritance from one parent but not the other. Imprinted genes typically occur in dense clusters that contain few non-imprinted genes and therefore representative genes from the Adp critical region could be assayed to identify any imprinted domains. None of the genes analysed were found to be imprinted, however, suggesting that other explanations for the Adp phenotype must be considered.

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Epigenetic regulation of placental endocrine lineages and complications of pregnancy

Biochemical Society Transactions ◽

10.1042/bst20130002 ◽

2013 ◽

Vol 41 (3) ◽

pp. 701-709 ◽

Cited By ~ 27

Author(s):

Rosalind M. John

Keyword(s):

Genomic Imprinting ◽

Giant Cells ◽

In Utero ◽

Imprinted Genes ◽

Endocrine Organ ◽

Fetal Physiology ◽

Trophoblast Giant Cells ◽

In Utero Development ◽

Genetic Conflicts

A defining feature of mammals is the development in utero of the fetus supported by the constant flow of nutrients from the mother obtained via a specialized organ: the placenta. The placenta is also a major endocrine organ that synthesizes vast quantities of hormones and cytokines to instruct both maternal and fetal physiology. Nearly 20 years ago, David Haig and colleagues proposed that placental hormones were likely targets of the epigenetic process of genomic imprinting in response to the genetic conflicts imposed by in utero development [Haig (1993) Q. Rev. Biol. 68, 495–532]. There are two simple mechanisms through which genomic imprinting could regulate placental hormones. First, imprints could directly switch on or off alleles of specific genes. Secondly, imprinted genes could alter the expression of placental hormones by regulating the development of placental endocrine lineages. In mice, the placental hormones are synthesized in the trophoblast giant cells and spongiotrophoblast cells of the mature placenta. In the present article, I review the functional role of imprinted genes in regulating these endocrine lineages, which lends support to Haig's original hypothesis. I also discuss how imprinting defects in the placenta may adversely affect the health of the fetus and its mother during pregnancy and beyond.

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

Epigenetics ◽

10.4161/epi.5.2.11081 ◽

2010 ◽

Vol 5 (2) ◽

pp. 149-158 ◽

Cited By ~ 13

Author(s):

Ismail Zaitoun ◽

Karen M. Downs ◽

Guilherme J. M. Rosa ◽

Hasan Khatib

Keyword(s):

Gene Expression ◽

Genomic Imprinting ◽

Imprinted Genes ◽

Insight Into

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Genetic conflict, genomic imprinting and establishment of the epigenotype in relation to growth

Reproduction ◽

10.1530/rep.0.1220185 ◽

2001 ◽

pp. 185-193 ◽

Cited By ~ 48

Author(s):

T Moore

Keyword(s):

Genomic Imprinting ◽

Parental Investment ◽

Tandem Repeats ◽

Cpg Islands ◽

Subsequent Development ◽

Imprinted Genes ◽

Growth Disorders ◽

Genetic Loci ◽

Mammalian Embryo ◽

Genetic Conflict

Genomic imprinting is the process that differentially modifies the parental alleles at certain genetic loci in the parental germlines. Such modifications of DNA and chromatin are somatically heritable and cause unequal expression of the parental alleles during subsequent development. In mammals, imprinted genes encode a relatively small number of functionally heterogeneous proteins. Nevertheless, imprinted genes exert important effects, primarily on fetal development, and their deregulation is implicated in a variety of pathologies including sporadic, inherited and induced growth disorders. Imprinted loci show several unusual structural and functional characteristics that may be related to mechanistic aspects of mono-allelic expression or to modes of evolution of imprinted genetic loci. Typically, imprinted genes are clustered in certain genomic regions and have relatively reduced intronic DNA content relative to non-imprinted genes. In addition, their regulatory regions frequently contain a combination of features including tandem repeats associated with differentially methylated CpG islands and overlapping transcription of coding or non-coding RNAs. The evolution of imprinting can be understood as the stable outcome of sexual selection acting differently on the parental alleles of genes that influence parental investment in offspring. Consistent with this explanation, imprinted genes are expressed predominantly during embryonic and postnatal development in mammals and in the developing endosperm of plants, and maternal or paternal expression at imprinted loci is associated with reduced or increased parental investment, respectively. Such selective forces have implications for understanding mechanistic aspects of genome reprogramming in the early mammalian embryo.

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Epigenetic Mechanisms of Genomic Imprinting: Common Themes in the Regulation of Imprinted Regions in Mammals, Plants, and Insects

Genetics Research International ◽

10.1155/2012/585024 ◽

2012 ◽

Vol 2012 ◽

pp. 1-17 ◽

Cited By ~ 18

Author(s):

William A. MacDonald

Keyword(s):

Genomic Imprinting ◽

Chromosomal Region ◽

Epigenetic Inheritance ◽

Imprinted Genes ◽

Epigenetic Mechanisms ◽

Research Model ◽

Primary Research ◽

Specific Expression ◽

Broad Variety ◽

Control Regions

Genomic imprinting is a form of epigenetic inheritance whereby the regulation of a gene or chromosomal region is dependent on the sex of the transmitting parent. During gametogenesis, imprinted regions of DNA are differentially marked in accordance to the sex of the parent, resulting in parent-specific expression. While mice are the primary research model used to study genomic imprinting, imprinted regions have been described in a broad variety of organisms, including other mammals, plants, and insects. Each of these organisms employs multiple, interrelated, epigenetic mechanisms to maintain parent-specific expression. While imprinted genes and imprint control regions are often species and locus-specific, the same suites of epigenetic mechanisms are often used to achieve imprinted expression. This review examines some examples of the epigenetic mechanisms responsible for genomic imprinting in mammals, plants, and insects.

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Multiple Imprinted Genes Associated with Prader-Willi Syndrome and Location of an Imprinting Control Element

Acta geneticae medicae et gemellologiae twin research ◽

10.1017/s000156600000115x ◽

1996 ◽

Vol 45 (1-2) ◽

pp. 87-89

Author(s):

R.D. Nicholls ◽

M.T.C. Jong ◽

C.C. Glenn ◽

J. Gabriel ◽

P.K. Rogan ◽

...

Keyword(s):

Genomic Imprinting ◽

Epigenetic Modification ◽

Uniparental Disomy ◽

Paternal Allele ◽

Control Element ◽

Parental Origin ◽

Imprinted Genes ◽

Mammalian Development ◽

Specific Expression ◽

Large Deletions

Our studies aim to identify the mechanisms and genes involved in genomic imprinting in mammalian development and human disease. Imprinting refers to an epigenetic modification of DNA that results in parent-of-origin specific expression during embryogenesis and in the adult. This imprint is reset at each generation, depending on the sex of the parental gametogenesis. Prader-Willi (PWS) and Angelman (AS) syndromes are excellent models for the study of genomic imprinting in humans, since these distinct neurobehavioural disorders are both associated with genetic abnormalities (large deletions, uniparental disomy, and imprinting mutations) of inheritance in chromosome 15q11-q13, dependent on the parental origin (reviewed in ref. 1). Some AS patients have biparental inheritance, consistent with a single imprinted gene (active on the maternal chromosome), whereas similar PWS patients are not found suggesting that at least two imprinted genes (active on the paternal allele) may be necessary for classical PWS. We have previously shown that the small ribonucleoprotein associated protein SmN gene (SNRPN), located in the PWS critical region [2], is only expressed from the paternal allele and is differentially methylated on parental alleles [3]. Therefore, SNRPN may have a role in PWS. Methylation imprints have also been found at two other loci in 15q11-q13, PW71 [4] and D15S9 [5], which map 120 kb and 1.5 Mb proximal to SNRPN, respectively. We have now characterized in detail the gene structure and expression from two imprinted loci within 15q11-q13, SNRPN and D15S9, which suggests that both loci are surprisingly complex, with important implications for the pathogenesis of PWS.

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