Search results for "Genomic Imprinting"

Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mec…

2014

Genomic imprinting is a form of epigenetic regulation that results in the expression of either the maternally or paternally inherited allele of a subset of genes (Ramowitz and Bartolomei 2011). This imprinted expression of transcripts is crucial for normal mammalian development. In humans, loss-of-imprinting of specific loci results in a number of diseases exemplified by the reciprocal growth phenotypes of the Beckwith-Wiedemann and Silver-Russell syndromes, and the behavioral disorders Angelman and Prader-Willi syndromes (Kagami et al. 2008; Buiting 2010; Choufani et al. 2010; Eggermann 2010; Kelsey 2010; Mackay and Temple 2010). In addition, aberrant imprinting also contributes to multige…

The placenta: phenotypic and epigenetic modifications induced by Assisted Reproductive Technologies throughout pregnancy

2015

International audience; Today, there is growing interest in the potential epigenetic risk related to assisted reproductive technologies (ART). Much evidence in the literature supports the hypothesis that adverse pregnancy outcomes linked to ART are associated with abnormal trophoblastic invasion. The aim of this review is to investigate the relationship between epigenetic dysregulation caused by ART and subsequent placental response. The dialogue between the endometrium and the embryo is a crucial step to achieve successful trophoblastic invasion, thus ensuring a non-complicated pregnancy and healthy offspring. However, as described in this review, ART could impair both actors involved in t…

Germline correction of an epimutation related to Silver-Russell syndrome.

2015

Like genetic mutations, DNA methylation anomalies or epimutations can disrupt gene expression and lead to human diseases. However, unlike genetic mutations, epimutations can in theory be reverted through developmental epigenetic reprograming, which should limit their transmission across generations. Following the request for a parental project of a patient diagnosed with Silver-Russell syndrome (SRS), and the availability of both somatic and spermatozoa DNA from the proband and his father, we had the exceptional opportunity to evaluate the question of inheritance of an epimutation. We provide here for the first time evidence for efficient reversion of a constitutive epimutation in the sperm…

The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4

2019

Abstract Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4–Not complex conditions its post-transcriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 acti…

Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast

2020

ABSTRACTGene expression involving RNA polymerase II is regulated by the concerted interplay between mRNA synthesis and degradation, crosstalk in which mRNA decay machinery and transcription machinery respectively impact transcription and mRNA stability. Rpb4, and likely dimer Rpb4/7, seem the central components of the RNA pol II governing these processes. In this work we unravel the molecular mechanisms participated by Rpb4 that mediate the posttranscriptional events regulating mRNA imprinting and stability. By RIP-Seq, we analyzed genome-wide the association of Rpb4 with mRNAs and demonstrated that it targeted a large population of more than 1400 transcripts. A group of these mRNAs was als…

ADHD and DAT1: Further evidence of paternal over-transmission of risk alleles and haplotype

2010

Contains fulltext : 87259.pdf (Publisher’s version ) (Closed access) We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD. The IMAGE sample, the largest of the three-replication samples, provides strong support for a parent of origin effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR, respectively) of DAT1. In addition, a similar pattern of over-transmission of paternal ri…

2015

AbstractGenomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels co…

Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis

2015

Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms t…

Genomic conflicts and sexual antagonism in human health: Insights from oxytocin and testosterone

2015

We review the hypothesized and observed effects of two of the major forms of genomic conflicts, genomic imprinting and sexual antagonism, on human health. We focus on phenotypes mediated by peptide and steroid hormones (especially oxytocin and testosterone) because such hormones centrally mediate patterns of physical and behavioral resource allocation that underlie both forms of conflict. In early development, a suite of imprinted genes modulates the human oxytocinergic system as predicted from theory, with paternally inherited gene expression associated with higher oxytocin production, and increased solicitation to mothers by infants. This system is predicted to impact health through the i…

Developments in the evolutionary theory of social interactions

2016

Altruistic behaviour, which benefits others but harms the actor, can evolve when copies of the underlying genes are transmitted to future generations by related beneficiaries. While we know that the mechanism of ‘kin selection’ answers to how altruism can evolve, the answers to why and when it can evolve are still obscure. The first aim of this thesis is to shed light to the evolution of altruism by identifying factors that facilitate or promote it. I find that the conditions under which altruism can evolve follow surprisingly simple principles that are independent of the taxon-specific traits such as fecundity. Further, by analysing the unique aspects of haplodiploid sex determination syst…