14 research outputs found

    Specific DNMT3C flanking sequence preferences facilitate methylation of young murine retrotransposons.

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    The DNA methyltransferase DNMT3C appeared as a duplication of the DNMT3B gene in muroids and is required for silencing of young retrotransposons in the male germline. Using specialized assay systems, we investigate the flanking sequence preferences of DNMT3C and observe characteristic preferences for cytosine at the -2 and -1 flank that are unique among DNMT3 enzymes. We identify two amino acids in the catalytic domain of DNMT3C (C543 and V547) that are responsible for the DNMT3C-specific flanking sequence preferences and evolutionary conserved in muroids. Reanalysis of published data shows that DNMT3C flanking preferences are consistent with genome-wide methylation patterns in mouse ES cells only expressing DNMT3C. Strikingly, we show that CpG sites with the preferred flanking sequences of DNMT3C are enriched in murine retrotransposons that were previously identified as DNMT3C targets. Finally, we demonstrate experimentally that DNMT3C has elevated methylation activity on substrates derived from these biological targets. Our data show that DNMT3C flanking sequence preferences match the sequences of young murine retrotransposons which facilitates their methylation. By this, our data provide mechanistic insights into the molecular co-evolution of repeat elements and (epi)genetic defense systems dedicated to maintain genomic stability in mammals

    Tidal energy redistribution among vertical modes in a fluid with a mid-depth pycnocline

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    International audienceWe modeled internal tide generation above a high sinusoidal ridge in a fluid with a mid-depth pycnocline and developed an original method to quantify internal tide vertical mode amplitude in two-dimensional-vertical simulations. Since lowest modes can propagate over considerable distances, while high modes are more likely to dissipate locally, estimating the tidal energy distribution among vertical modes is necessary to investigate the spatial redistribution of the tidal energy. Our numerical approach allows expansion and verification of previous analytical studies over a larger range of configurations. The tidal energy distribution among vertical modes is shown here to be dependent on the topographic resonance criterion and the topographic blocking parameter

    A non-hydrostatic non-Boussinesq algorithm for free-surface ocean modelling

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    International audienceA three-mode time-split algorithm is proposed to simulate non-hydrostatic ocean processes in a natural way: fast pressure adjustments via acoustic waves are explicitly represented. The full set of compressible Navier-Stokes equations is integrated for a free-surface ocean with three time-steps respectively associated to the internal, external and compressible (non Boussinesq) modes. The resulting three-mode algorithm can be implemented either in a fully compressible configuration or in a "pseudo-compressible" configuration by artificially lowering acoustic-wave velocities to reduce computational costs. The present description of the three-mode algorithm focuses in the first place on the simulation of non-hydrostatic processes in free-surface ocean models. Several test simulations related to linear and non-linear acoustic, surface and internal gravity waves are studied in details with the proposed three-mode algorithm

    Photosensitized oxidative addition to gold(i) enables alkynylative cyclization of o-alkylnylphenols with iodoalkynes

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    International audienceThe well-established oxidative addition-reductive elimination pathway is the most followed one in transition metal catalyzed cross coupling reactions. While readily occurring with a series of transition metals, it does not take place with gold(I) complexes which have shown some reluctance to undergo oxidative addition unless special sets of ligands on gold(I), reagents or reaction conditions are used. A new possibility to overcome this hurdle has been devised. Upon visible light irradiation, an iridium photocatalyst triggers via triplet sensitization the oxidative addition of an al-kynyliodide onto a vinylgold(I) intermediate to deliver Csp 2-Csp coupling products after reductive elimination. Mechanistic and modeling studies support that an energy transfer takes place and not a redox pathway. This novel mode of activation in gold homogenous catalysis was applied in several dual catalytic processes. Alkynylbenzofuran derivatives were obtained from o-alkynylphenols and iodoalkynes in the presence of catalytic gold(I) and iridium(III) complexes under blue LED irradiation. Over the last two decades, homogeneous gold catalysis has been extensively used to efficiently and selectively promote a variety of cyclization processes. 1-3 The typical casting involves bifunctional substrates bearing an unsaturation prompt to electrophilic activation and a judiciously positioned internal nucleophile. A protodemetalation of the organogold intermediates to afford hydrofunctional-ized products generally terminates the catalytic cycles. 4 Pursuing the step economy principle and also aiming at higher level of molecular complexity, some in situ post-functionalization reactions of the organogold 5 intermediate have been devised such as electrophilic halogenation or cross-coupling reactions. Although palladium catalyzed cross coupling from an organogold(I) intermediate has bee
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