H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation

Epigenetic mechanisms play diverse roles in the regulation of genome stability in eukaryotes. In Arabidopsis thaliana, genome stability is maintained during DNA replication by the H3.1K27 methyltransferases ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) and ATXR6, which catalyze the deposition of K27me1 on replication-dependent H3.1 variants. The loss of H3.1K27me1 in atxr5 atxr6 double mutants leads to heterochromatin defects, including transcriptional de-repression and genomic instability, but the molecular mechanisms involved remain largely unknown. In this study, we identified the transcriptional co-activator and conserved histone acetyltransferase GCN5 as a mediator of transcriptional de-repression and genomic instability in the absence of H3.1K27me1. GCN5 is part of a SAGA-like complex in plants that requires the GCN5-interacting protein ADA2b and the chromatin remodeler CHR6 to mediate the heterochromatic defects in atxr5 atxr6 mutants. Our results also indicate that Arabidopsis GCN5 acetylates multiple lysine residues on H3.1 variants, but H3.1K27 and H3.1K36 play essential functions in inducing genomic instability in the absence of H3.1K27me1. Finally, we show that H3.1K36 acetylation by GCN5 is negatively regulated by H3.1K27me1 in vitro. Overall, this work reveals a key molecular role for H3.1K27me1 in maintaining transcriptional silencing and genome stability in heterochromatin by restricting GCN5-mediated histone acetylation in plants

The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication

The tail of replication-dependent histone H3.1 varies from that of replication-independent H3.3 at the amino acid located at position 31 in plants and animals, but no function has been assigned to this residue to demonstrate a unique and conserved role for H3.1 during replication. Here, we show that TONSOKU (TSK/TONSL), which rescues broken replication forks, specifically interacts with H3.1 via recognition of alanine 31 by its tetratricopeptide repeat domain. Our results indicate that genomic instability in the absence of ATXR5/ATXR6-catalyzed H3K27me1 in plants depends on H3.1, TSK and DNA polymerase theta (Pol θ). Overall, this work reveals an H3.1-specific function during replication and the common strategy used in multicellular eukaryotes for regulating post-replicative chromatin maturation and TSK, which relies on histone mono-methyltransferases and reading the H3.1 variant

Immune Responses Elicited in Tertiary Lymphoid Tissues Display Distinctive Features

During chronic inflammation, immune effectors progressively organize themselves into a functional tertiary lymphoid tissue (TLT) within the targeted organ. TLT has been observed in a wide range of chronic inflammatory conditions but its pathophysiological significance remains unknown. We used the rat aortic interposition model in which a TLT has been evidenced in the adventitia of chronically rejected allografts one month after transplantation. The immune responses elicited in adventitial TLT and those taking place in spleen and draining lymph nodes (LN) were compared in terms of antibody production, T cell activation and repertoire perturbations. The anti-MHC humoral response was more intense and more diverse in TLT. This difference was associated with an increased percentage of activated CD4+ T cells and a symmetric reduction of regulatory T cell subsets. Moreover, TCR repertoire perturbations in TLT were not only increased and different from the common pattern observed in spleen and LN but also “stochastic,” since each recipient displayed a specific pattern. We propose that the abnormal activation of CD4+ T cells promotes the development of an exaggerated pathogenic immune humoral response in TLT. Preliminary findings suggest that this phenomenon i) is due to a defective immune regulation in this non-professional inflammatory-induced lymphoid tissue, and ii) also occurs in human chronically rejected grafts

Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner

Étude ostéomorphométrique d’ensembles crâniens d’oiseaux sauvages autochtones non captifs de l’Ouest de la France :variabilité intra- et interspécifique

International audienceThe osteology of Western France birds is far from being well known. This study is based on a sample of more than 100 species and 800 individuals collected at the “Centre Vétérinaire de la Faune Sauvage et des Écosystèmes des Pays de la Loire” (Nantes). It is founded on 38 skull dimensions, including jaw bones. The results allowed a uni- and multivariate statistical study. A sexual dimorphism was shown for three species, and species or families could be differentiated within many orders.L’ostéologie des oiseaux de l’Ouest de la France est assez mal connue. Cette étude s’appuie sur un échantillon de plus de 100 espèces pour 800 individus recueillis au sein du Centre Vétérinaire de la Faune Sauvage et des Écosystèmes des Pays de la Loire (Nantes). Elle se fonde sur 38 dimensions crâniennes, intégrant les mandibules. Les résultats obtenus ont permis une analyse statistique uni- et multivariée. Un dimorphisme sexuel a été montré pour trois espèces. Certaines espèces ou familles ont pu être discriminées au sein de nombreux ordres

Irradiation of fish embryos prior to blastomere transfer boosts the colonisation of their gonads by donor-derived gametes.

Blastomere transplantation into fish blastula embryos results in somatic chimeras, which generally provide null or a small proportion of gametes derived from the donor. This may partly explain why none of the ES-like cell lines established from fish embryos has contributed to the germline of chimeras when transplanted at the blastula stage. Here, we report that a moderate gamma-irradiation of recipient embryos, followed by transplantation of dispersed blastomeres, considerably enhances the proportion of donor-derived gametes (53% versus 5% in average). In fish, the resulting protocol should maximise the pluripotency level measured in vivo for embryonic cell lines and for cultured germ cells

Viscosity and self-diffusion of supercooled and stretched water from molecular dynamics simulations

Among the numerous anomalies of water, the acceleration of dynamics under pressure is particularly puzzling. Whereas the diffusivity anomaly observed in experiments has been reproduced in several computer studies, the parallel viscosity anomaly has received less attention. Here we simulate viscosity and the self-diffusion coefficient of the TIP4P/2005 water model over a broad temperature and pressure range. We reproduce the experimental behavior and find additional anomalies at negative pressure. The anomalous effect of pressure on dynamic properties becomes more pronounced upon cooling, reaching two orders of magnitude for viscosity at 220 K. We analyze our results with a dynamic extension of a thermodynamic two-state model, an approach which has proved successful in describing experimental data. Water is regarded as a mixture of interconverting species with contrasting dynamic behaviors, one being strong (Arrhenius) and the other fragile (non-Arrhenius). The dynamic parameters of the two-state models are remarkably close between experiment and simulations. The larger pressure range accessible to simulations suggests a modification of the dynamic two-state model, which in turn also improves the agreement with experimental data. Furthermore, our simulations demonstrate the decoupling between viscosity eta and self-diffusion coefficient D as a function of temperature T. The Stokes-Einstein relation, which predicts a constant D eta/T, is violated when T is lowered, in connection with the Widom line defined by an equal fraction of the two interconverting species. These results provide a unifying picture of thermodynamics and dynamics in water and call for experiments at negative pressure. Published by AIP Publishing