Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size.

OBJECTIVES: To study DNA methylation at the C19MC locus in the placenta and its association with (1) parental body size, (2) transmission of haplotypes for the C19MC rs55765443 SNP, and (3) offspring's body size and/or body composition at birth and in childhood. SUBJECTS AND METHODS: Seventy-two pregnant women-infant pairs and 63 fathers were included in the study. Weight and height of mothers, fathers and newborns were registered during pregnancy or at birth (n = 72). Placental DNA methylation at the C19MC imprinting control region (ICR) was quantified by bisulfite pyrosequencing. Genotyping of the SNP was performed using restriction fragment length polymorphisms. The children's body size and composition were reassessed at age 6 years (n = 32). RESULTS: Lower levels of placental C19MC methylation were associated with increased body size of mother, specifically with higher pregestational and predelivery weights and height of the mother (β from -0.294 to -0.371; R2 from 0.04 to 0.10 and all p < 0.019), and with higher weight, height, waist and hip circumferences, and fat mass of the child (β from -0.428 to -0.552; R2 from 0.33 to 0.56 and all p < 0.009). Parental transmission of the SNP did not correlate with an altered placental methylation status at the C19MC ICR. CONCLUSIONS: Increased maternal size is associated with reduced placental C19MC methylation, which, in turn, relate to larger body size of the child.This study was supported by grants from the Ministerio de Ciencia e Innovación, Instituto de 10 Salud Carlos III (ISCIII), Madrid, Spain (PI17/00557 to JB, and PI13/01257 and PI16/01335 to AL-B), projects co-funded by FEDER (Fondo Europeo de Desarrollo Regional). RF and MG acknowledge grant funding from the Fondation pour la Recherche Médicale (Equipes FRM, 13 grant number DEQ31703)

Whole-Genome Analysis Reveals That Active Heat Shock Factor Binding Sites Are Mostly Associated with Non-Heat Shock Genes in Drosophila melanogaster

During heat shock (HS) and other stresses, HS gene transcription in eukaryotes is up-regulated by the transcription factor heat shock factor (HSF). While the identities of the major HS genes have been known for more than 30 years, it has been suspected that HSF binds to numerous other genes and potentially regulates their transcription. In this study, we have used a chromatin immunoprecipitation and microarray (ChIP-chip) approach to identify 434 regions in the Drosophila genome that are bound by HSF. We have also performed a transcript analysis of heat shocked Kc167 cells and third instar larvae and compared them to HSF binding sites. The heat-induced transcription profiles were quite different between cells and larvae and surprisingly only about 10% of the genes associated with HSF binding sites show changed transcription. There were also genes that showed changes in transcript levels that did not appear to correlate with HSF binding sites. Analysis of the locations of the HSF binding sites revealed that 57% were contained within genes with approximately 2/3rds of these sites being in introns. We also found that the insulator protein, BEAF, has enriched binding prior to HS to promoters of genes that are bound by HSF upon HS but that are not transcriptionally induced during HS. When the genes associated with HSF binding sites in promoters were analyzed for gene ontology terms, categories such as stress response and transferase activity were enriched whereas analysis of genes having HSF binding sites in introns identified those categories plus ones related to developmental processes and reproduction. These results suggest that Drosophila HSF may be regulating many genes besides the known HS genes and that some of these genes may be regulated during non-stress conditions

Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav

Génétique moléculaire de la coloration (découverte d'un allèle A(br) du gène Agouti responsable de la bringeure de la race bovine Normande)

L'objectif de ce projet de recherche est l'identification de marqueurs moléculaires dans les gènes de coloration qui pourraient être utilisés pour la traçabilité des produits d'origine bovine. Parmi les gènes de coloration, Agouti code pour une protéine antagoniste de la fixation de l'hormone a-MSH sur le récepteur aux mélanocortines 1 (Mc1r), codé par le gène Extension, et permet le " switch " de la synthèse d'eumélanine (noir/marron) vers la synthèse de pheomélanine (jaune/rouge), dans les mélanocytes de la peau. Nous démontrons dans ce travail que trois promoteurs alternatifs dirigent l'expression de transcrits, porteurs de régions 5'UTRs différentes, dans de nombreux tissus, ce qui suggère un rôle probable d'Agouti dans différentes fonctions physiologiques, en plus de la coloration chez le bovin. La race Normande, de génotype Extension sauvage (E+/E+), a un phénotype bringé. La bringeure est une présence variable de poils noirs sur un fond coloré rouge/brun. Le gène Agouti est surexprimé chez la Normande. Un élément de type LINE, inséré dans la région 5' génomique, provoque la surexpression de transcrits alternatifs. Le niveau de méthylation de l'élément LINE est responsable de la répression aléatoire du gène Agouti dans la peau Normande. Ce nouvel allèle Agouti (Abr) est présent à l'état homozygote dans la race Normande. Enfin, l'immunodétection dans la peau bovine a révélé une forme libre tétramérique de la protéine Agouti et une forme liée à une protéine de grande tailleLIMOGES-BU Sciences (870852109) / SudocSudocFranceF

SOX9 has distinct regulatory roles in alternative splicing and transcription

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Analysis of the progression of JAK2 V617F positive myeloproliferative neoplasms by single-nucleotide polymorphism array does not reveal a strong chromosomal instability

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Directed self-assembly of PS-b-PDMS into 193nm photoresist patterns and transfer into silicon by plasma etching

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PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome

Symmetrical dimethylation on arginine-3 of histone H4 (H4R3me2s) has been reported to occur at several repressed genes, but its specific regulation and genomic distribution remained unclear. Here, we show that the type-II protein arginine methyltransferase PRMT5 controls H4R3me2s in mouse embryonic fibroblasts (MEFs). In these differentiated cells, we find that the genome-wide pattern of H4R3me2s is highly similar to that in embryonic stem cells. In both the cell types, H4R3me2s peaks are detected predominantly at G + C-rich regions. Promoters are consistently marked by H4R3me2s, independently of transcriptional activity. Remarkably, H4R3me2s is mono-allelic at imprinting control regions (ICRs), at which it marks the same parental allele as H3K9me3, H4K20me3 and DNA methylation. These repressive chromatin modifications are regulated independently, however, since PRMT5-depletion in MEFs resulted in loss of H4R3me2s, without affecting H3K9me3, H4K20me3 or DNA methylation. Conversely, depletion of ESET (KMT1E) or SUV420H1/H2 (KMT5B/C) affected H3K9me3 and H4K20me3, respectively, without altering H4R3me2s at ICRs. Combined, our data indicate that PRMT5-mediated H4R3me2s uniquely marks the mammalian genome, mostly at G + C-rich regions, and independently from transcriptional activity or chromatin repression. Furthermore, comparative bioinformatics analyses suggest a putative role of PRMT5-mediated H4R3me2s in chromatin configuration in the nucleus