Multiple modes of PRC2 inhibition elicit global chromatin alterations in H3K27M pediatric glioma

A methionine substitution at lysine-27 on histone H3 variants (H3K27M) characterizes ~80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits polycomb repressive complex 2 (PRC2) in a dominant-negative fashion. Yet, the mechanisms for this inhibition and abnormal epigenomic landscape have not been resolved. Using quantitative proteomics, we discovered that robust PRC2 inhibition requires levels of H3K27M greatly exceeding those of PRC2, seen in DIPG. While PRC2 inhibition requires interaction with H3K27M, we found that this interaction on chromatin is transient, with PRC2 largely being released from H3K27M. Unexpectedly, inhibition persisted even after PRC2 dissociated from H3K27M-containing chromatin, suggesting a lasting impact on PRC2. Furthermore, allosterically activated PRC2 is particularly sensitive to H3K27M, leading to the failure to spread H3K27me from PRC2 recruitment sites and consequently abrogating PRC2's ability to establish H3K27me2-3 repressive chromatin domains. In turn, levels of polycomb antagonists such as H3K36me2 are elevated, suggesting a more global, downstream effect on the epigenome. Together, these findings reveal the conditions required for H3K27M-mediated PRC2 inhibition and reconcile seemingly paradoxical effects of H3K27M on PRC2 recruitment and activity

Rétention de l'uranium et de l'europium sur la pyrite

Congrès le 7 et 8 Septembre 2006. Communications Orales

Uranium (VI) interaction with pyrite (FeS2): chemical and spectroscopic studies.

International audienceThe mechanism of uranium(VI) interaction with pyrite was studied by solution chemistry and X-ray Photoelectron Spectroscopy (XPS). Natural pyrite was characterized by X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). After equilibration in 10(-2) moI L-1 NaNO3, pyrite was reacted with uranium(VI) by the batch method in an anoxic glove box (P-O2 < 1 ppm) at ambient temperature. The reaction products of uranium, iron and sulphur were characterized (oxidation state, chemical environment) by XPS. Quantitative analysis revealed that only a few atomic percent of uranium is retained at the pyrite surface. The U4f core level binding energies are consistent with the coexistence of an uranium(VI) species and of uranium in a reduced form. No sulphur oxidation products were observed by XPS, but spectral decomposition of the Fe 2p lines revealed the presence of iron(III) oxide or (oxy)hydroxide. These results seem to point to a redox reaction between uraniurn(VI) and pyrite

Interaction de l'uranium (VI) avec la pyrite (FeS2).

Communications Orale

Interaction de l'uranium (VI) et de la pyrite (FeS2)

Conférence les 10 et 11 mars 2005. Communication par affiche

Uptake of uranium and trace elements in pyrite (FeS₂) suspensions

International audiencePyrite dissolution and interaction with Fe(II), Co(II), Eu(III) and U(VI) have been studied under anoxic conditions by solution chemistry and spectroscopic techniques. Aqueous data show a maximal cation uptake above pH 5.5. Iron (II) uptake can explain the non-stoichiometric [S]aq/[Fe]aq ratios often observed during dissolution experiments. Protonation data corrected for pyrite dissolution resulted in a proton site density of 9&nbsp;±&nbsp;3&nbsp;sites&nbsp;nm−2. Concentration isotherms for Eu(III) and U(VI) sorption on pyrite indicate two different behaviours which can be related to the contrasted redox properties of these elements. For Eu(III), sorption can be explained by the existence of a unique site with a saturation concentration of 1.25&nbsp;×&nbsp;10−6&nbsp;mol&nbsp;g−1. In the U(VI) case, sorption seems to occur on two different sites with a total saturation concentration of 4.5&nbsp;×&nbsp;10−8&nbsp;mol&nbsp;g−1. At lower concentration, uranium reduction occurs, limiting the concentration of dissolved uranium to the solubility of UO2(s).Scanning electron microscopy and micro-Raman spectrometry of U(VI)-sorbed pyrite indicate a heterogeneous distribution of U at the pyrite surface and a close association with oxidized S. X-ray photoelectron spectroscopy confirms the partial reduction of U and the formation of a hyperstoichiometric UO2+x(s). Our results are consistent with a chemistry of the pyrite surface governed not by Fe(II)-bound hydroxyl groups, but by S groups which can either sorb cations and protons, or sorb and reduce redox-sensitive elements such as U(VI)

Vibrational spectroscopy of synthetic analogues of ankoleite, chernikovite and intermediate solid solution

International audienceAnkoleite (K(UO 2)PO 4 ·nH 2 O), chernikovite (H 3 O(UO 2)PO 4 ·nH 2 O) and intermediate solid solutions are frequently encountered in the uranium ores that result from the alteration of uranium primary minerals. This paper reports a thorough FTIR and Raman study related to synthetic analogues for these minerals. First, the vibration bands associated to the UO 2 2+ uranyl ion were used to calculate the U=O bond length which appeared in good agreement with the data coming from PXRD. Then, the examination of the phosphate vibration modes in both sets of spectra confirmed the general formulation of the samples and ruled out the presence of hydrogenphosphate groups. Finally, the presence of H 2 O as well as protonated H 3 O + and/or H 5 O 2 + species was also pointed out, and could be used to clearly differentiate the various phases prepared. Vibrational spectroscopy then appeared as an efficient method for the investigation of such analogues of natural samples. It should be particularly relevant when identifying these phases in mineral ores or assemblies

Adsorption of radium and barium on goethite and ferrihydrite: A kinetic and surface complexation modelling study

AbstractRadium and barium uptake onto ferrihydrite and goethite have been studied in the concentration range 1nM to 5mM and from pH 4 to 10, to develop a model to predict radium behaviour in legacy uranium mining wastes. For ferrihydrite, uptake of Ra2+ at nM concentrations was strong at pH >7. At higher concentrations, Ba2+ sorption to ferrihydrite was slightly weaker than that of Ra2+. Experiments with goethite showed weaker binding for both metal ions in all systems. The interactions of radium with both ferrihydrite and goethite are fully reversible. The behaviour of radium during transformation of ferrihydrite to goethite has been studied, and no evidence for irreversible incorporation within the goethite lattice was found; radium uptake to goethite was the same, whether or not it was present during its formation. Calcium competed with radium for ferrihydrite sorption only at high calcium concentrations (>10mM). Barium is a more effective competitor, and a concentration of 1mM reduced radium sorption. Sediment samples from a legacy uranium mining site have been analysed, and the in situ Rd values are consistent with radium uptake by surface coatings of ferrihydrite or goethite like phases. Surface complexation models have been developed for radium sorption to ferrihydrite and goethite which simulate the experimental data successfully. In both cases, approaches based on a single surface functional group and tetradentate binding sites simulated the data successfully. These data could be used in underpinning the safety case for legacy mining sites