Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming.
Ontology highlight
ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC3193417 | biostudies-other | 2011 Mar
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Imprinted genes represent a curious defiance of normal Mendelian genetics. Mammals inherit two complete sets of chromosomes, one from the mother and one from the father, and most autosomal genes will be expressed from both the maternal and the paternal alleles. Imprinted genes, however, are expressed from only one chromosome, in a parent-of-origin-dependent manner. Because silent and active promoters are present in a single nucleus, the differences in activity cannot be explained by transcription-factor abundance. Thus, transcription of imprinted genes represents a clear situation in which epigenetic mechanisms restrict gene expression and, therefore, offers a model for understanding the role of DNA modifications and chromatin structure in maintaining appropriate patterns of expression. Furthermore, because of their parent-of-origin-restricted expression, phenotypes determined by imprinted genes are susceptible not only to genetic alterations in the genes but also to disruptions in the epigenetic programs controlling regulation. Imprinted genes are often associated with human diseases, including disorders affecting cell growth, development, and behavior.
| S-EPMC1287882 | biostudies-literature
Project description:Genomic imprinting depends on the establishment and maintenance of DNA methylation at imprinting control regions. However, the mechanisms by which these heritable marks influence allele-specific expression are not fully understood. By analyzing maternal, zygotic, maternal-zygotic, and conditional Trim28 mutants, we found that the transcription factor TRIM28 controls genomic imprinting through distinct mechanisms at different developmental stages. During early genome-wide reprogramming, both maternal and zygotic TRIM28 are required for the maintenance of methylation at germline imprints. However, in conditional Trim28 mutants, Gtl2-imprinted gene expression was lost despite normal methylation levels at the germline IG-DMR. These results provide evidence that TRIM28 controls imprinting after early embryonic reprogramming through a mechanism other than the maintenance of germline imprints. Additionally, our finding that secondary imprints were hypomethylated in TRIM28 mutants uncovers a requirement of TRIM28 after genome-wide reprogramming for interpreting germline imprints and regulating DNA methylation at imprinted gene promoters.
| S-EPMC4644443 | biostudies-literature
Project description:The epigenetic events that occur during the development of the mammalian embryo are essential for correct gene expression and cell-lineage determination. Imprinted genes are expressed from only one parental allele due to differential epigenetic marks that are established during gametogenesis. Several theories have been proposed to explain the role that genomic imprinting has played over the course of mammalian evolution, but at present it is not clear if a single hypothesis can fully account for the diversity of roles that imprinted genes play. In this review, we discuss efforts to define the extent of imprinting in the mouse genome, and suggest that different imprinted loci may have been wrought by distinct evolutionary forces. We focus on a group of small imprinted domains, which consist of paternally expressed genes embedded within introns of multiexonic transcripts, to discuss the evolution of imprinting at these loci.
| S-EPMC1657038 | biostudies-literature
Project description:Derivation of induced pluripotent stem (iPS) cells is mainly an epigenetic reprogramming process. It is still quite controversial how genomic imprinting is reprogrammed in iPS cells. Thus, we derived multiple iPS clones from genetically identical mouse somatic cells. We found that parentally inherited imprint was variably lost among these iPS clones. Concurrent with the loss of DNA methylation imprint at the corresponding Snrpn and Peg3 imprinted regions, parental origin-specific expression of the Snrpn and Zim1 imprinted genes was also lost in these iPS clones. This loss of parental genomic imprinting in iPS cells was likely caused by the reprogramming process during iPS cell derivation because extended culture of iPS cells did not lead to significant increase in the loss of genomic imprinting. Intriguingly, one to several paternal chromosomes appeared to have acquired de novo methylation at the Snrpn and Zac1 imprinted regions in a high percentage of iPS clones. These results might have some implications for future therapeutic applications of iPS cells. Since DNA methylation imprint can be completely erased in some iPS clones at multiple imprinted regions, iPS cell reprogramming may also be employed to dissect the underlying mechanisms of erasure, reacquisition and maintenance of genomic imprinting in mammals.
| S-EPMC3815550 | biostudies-literature
Project description: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.
| S-EPMC8168557 | biostudies-literature
Project description:Environmental factors can induce significant epigenetic changes that may also be inherited by future generations. The maternally inherited symbiont of arthropods Wolbachia pipientis is an excellent candidate as an 'environmental' factor promoting trans-generational epigenetic changes: by establishing intimate relationships with germ-line cells, epigenetic effects of Wolbachia symbiosis would be manifested as a 'maternal effect', in which infection of the mother modulates the offspring phenotype. In the leafhopper Zyginidia pullula, Wolbachia feminizes genetic males, leaving them as intersexes. With the exception of male chitinous structures that are present in the last abdominal segment, feminized males display phenotypic features that are typical of females. These include ovaries that range from a typical histological architecture to an altered structure. Methylation-sensitive random amplification of polymorphic DNA profiles show that they possess a female genomic imprint. On the other hand, some rare feminized males bear testes instead of ovaries. These specimens possess a Wolbachia density approximately four orders of magnitude lower than feminized males with ovaries and maintain a male genome-methylation pattern. Our results indicate that Wolbachia infection disrupts male imprinting, which dramatically influences the expression of genes involved in sex differentiation and development, and the alteration occurs only if Wolbachia exceeds a density threshold. Thus, a new Wolbachia's role as an environmental evolutionary force, inducing epigenetic trans-generational changes, should now be considered.
| S-EPMC2690474 | biostudies-literature
Project description:Progress in studying epigenetic reprogramming in plants has been impeded by the difficulty in obtaining tissue for analysis. Now, using a combination of fluorescent reporters and translational fusions, a new study sheds some light on this process.
| S-EPMC5569885 | biostudies-other
Project description:Many loci maintain parent-of-origin DNA methylation only briefly after fertilization during mammalian development: Whether this form of transient genomic imprinting can impact the early embryonic transcriptome or even have life-long consequences on genome regulation and possibly phenotypes is currently unknown. Here, we report a maternal germline differentially methylated region (DMR) at the mouse Gpr1/Zdbf2 (DBF-type zinc finger-containing protein 2) locus, which controls the paternal-specific expression of long isoforms of Zdbf2 (Liz) in the early embryo. This DMR loses parental specificity by gain of DNA methylation at implantation in the embryo but is maintained in extraembryonic tissues. As a consequence of this transient, tissue-specific maternal imprinting, Liz expression is restricted to the pluripotent embryo, extraembryonic tissues, and pluripotent male germ cells. We found that Liz potentially functions as both Zdbf2-coding RNA and cis-regulatory RNA. Importantly, Liz-mediated events allow a switch from maternal to paternal imprinted DNA methylation and from Liz to canonical Zdbf2 promoter use during embryonic differentiation, which are stably maintained through somatic life and conserved in humans. The Gpr1/Zdbf2 locus lacks classical imprinting histone modifications, but analysis of mutant embryonic stem cells reveals fine-tuned regulation of Zdbf2 dosage through DNA and H3K27 methylation interplay. Together, our work underlines the developmental and evolutionary need to ensure proper Liz/Zdbf2 dosage as a driving force for dynamic genomic imprinting at the Gpr1/Zdbf2 locus.
| S-EPMC3950344 | biostudies-literature
Project description:BACKGROUND:In plants, the existence and possible role of epigenetic reprogramming has been questioned because of the occurrence of stably inherited epialleles. Evidence suggests that epigenetic reprogramming does occur during land plant reproduction, but there is little consensus on the generality and extent of epigenetic reprogramming in plants. We studied DNA methylation dynamics during the life cycle of the liverwort Marchantia polymorpha. We isolated thalli and meristems from male and female gametophytes, archegonia, antherozoids, as well as sporophytes at early and late developmental stages, and compared their DNA methylation profiles. RESULTS:Of all cytosines tested for differential DNA methylation, 42% vary significantly in their methylation pattern throughout the life cycle. However, the differences are limited to few comparisons between specific stages of the life cycle and suggest four major epigenetic states specific to sporophytes, vegetative gametophytes, antherozoids, and archegonia. Further analyses indicated clear differences in the mechanisms underlying reprogramming in the gametophytic and sporophytic generations, which are paralleled by differences in the expression of genes involved in DNA methylation. Differentially methylated cytosines with a gain in methylation in antherozoids and archegonia are enriched in the CG and CHG contexts, as well as in gene bodies and gene flanking regions. In contrast, gain of DNA methylation during sporophyte development is mostly limited to the CHH context, LTR retrotransposons, DNA transposons, and repeats. CONCLUSION:We conclude that epigenetic reprogramming occurs at least twice during the life cycle of M. polymorpha and that the underlying mechanisms are likely different between the two events.
| S-EPMC5784723 | biostudies-literature
Project description:How phenomena like helping, dispersal, or the sex ratio evolve depends critically on demographic and life-history factors. One phenotype that is of particular interest to biologists is genomic imprinting, which results in parent-of-origin-specific gene expression and thus deviates from the predictions of Mendel's rules. The most prominent explanation for the evolution of genomic imprinting, the kinship theory, originally specified that multiple paternity can cause the evolution of imprinting when offspring affect maternal resource provisioning. Most models of the kinship theory do not detail how population subdivision, demography, and life history affect the evolution of imprinting. In this work, we embed the classic kinship theory within an island model of population structure and allow for diverse demographic and life-history features to affect the direction of selection on imprinting. We find that population structure does not change how multiple paternity affects the evolution of imprinting under the classic kinship theory. However, if the degree of multiple paternity is not too large, we find that sex-specific migration and survival and generation overlap are the primary factors determining which allele is silenced. This indicates that imprinting can evolve purely as a result of sex-related asymmetries in the demographic structure or life history of a species.
| S-EPMC2989731 | biostudies-literature