Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells

BACKGROUND: Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear. METHODS AND FINDINGS: Here, we show that the expression level of Hoxa9 is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive histone modifications co-exist along the Hoxa9 regulatory region. We further demonstrate that both Cdx4 and menin bind to the same regulatory region at the Hoxa9 locus in vivo, and co-activate the reporter gene driven by the Hoxa9 cis-elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access to the chromatin target and significantly reduces both active and repressive histone H3 modifications in the Hoxa9 locus. CONCLUSION: These results suggest a functional link among Cdx4, menin and histone modifications in Hoxa9 regulation in hematopoietic cells

Effet des acides organiques sur l’indice écotoxique des mâchefers d’incinération d’ordures ménagères (Miom)

In France, incineration, with or without heat recovery, handles about 50% of municipal waste. The main by-product of the process is the bottom ash. Bottom ash disposal is regulated by a directive that allows or not the disposal. The bottom ash must undergo physico- chemical tests and depending on the results are sorted into different classes allowing the re-use or not. This study shows that it is difficult to find a directcorrelation between the well studied leaching and physico- chemical tests and the biotest response. However, we find a correlation between the carboxylic acids amount and the ecotoxicologic index for the bottom ash. These results demonstrate that organic carbon caracterisation in the bottom ash is needed if one wants to have a coherent sorting procedure for the bottom ashes.En France, l’incinération (avec ou sans récupération d’énergie) traite près de 50 % des déchets ménagers. Le principal sous-produit (en poids) issu de l’incinération est le mâchefer. La gestion du mâchefer a été encadrée par une circulaire qui permet son classement. Les mâchefers doivent subir différents tests physico-chimiques et peuvent être ainsi classés dans une catégorie permettant leur valorisation ou non. Dans cette étude il nous a semblé intéressant de coupler cette caractérisation physico-chimique avec des tests biologiques pour apporter une nouvelle approche de caractérisation du mâchefer. Cette étude a permis de montrer qu’il est difficile d’effectuer une corrélation directe entre les caractéristiques physico-chimiques du mâchefer (habituellement étudiées) et leurs réponses aux biotests. Par contre, il existerait une relation entre leur teneur en acides carboxyliques et l’indice écotoxique de chacun des mâchefers. Ces résultats montrent que la caractérisation du carbone organique présent dans les mâchefers est nécessaire pour élaborer un classement cohérent entre les résultats obtenus lors de la caractérisation physico-chimique du Miom et les indices d’écotoxicité calculés à partir des différents biotests réalisés sur les mâchefers

Precursor effect on Mn-Fe-Ce/TiO₂ catalysts for selective catalytic reduction of no with NH₃ at low temperatures

Preparation of Mn/TiO2, Mn-Fe/TiO2, and Mn-Fe-Ce/TiO2 by the deposition-precipitation (DP) method can afford very active catalysts for low-temperature NH3-SCR (selective catalytic reduction of NO with NH3). The effect of precursor choice (nitrate vs. acetate) of Mn, Fe, and Ce on the physiochemical properties including thermal stability and the resulting SCR activity were investigated. The resulting materials were characterized by N2-Physisorption, XRD (Powder X-ray diffraction), XPS (X-ray photoelectron spectroscopy), H2-TPR (temperature-programmed reduction with hydrogen), and the oxidation of NO to NO2 measured at 300 °C. Among all the prepared catalysts 5MnAce/Ti, 25Mn0.75AceFe0.25Nit/Ti, and 25Mn0.75AceFe0.20NitCe0.05Ace/Ti showed superior SCR activity at low temperature. The superior activity of the latter two materials is likely attributable to the presence of amorphous active metal oxide phases (manganese-, iron- and cerium-oxide) and the ease of the reduction of metal oxides on TiO2. Enhanced ability to convert NO to NO2, which can promote fast-SCR like pathways, could be another reason. Cerium was found to stabilize amorphous manganese oxide phases when exposed to high temperatures

The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis

The homeobox transcription factor CDX2 plays an important role in embryonic development and regulates the proliferation and differentiation of intestinal epithelial cells in the adult. We have found that CDX2 is expressed in leukemic cells of 90% of patients with acute myeloid leukemia (AML) but not in hematopoietic stem and progenitor cells derived from normal individuals. Stable knockdown of CDX2 expression by RNA interference inhibited the proliferation of various human AML cell lines and strongly reduced their clonogenic potential in vitro. Primary murine hematopoietic progenitor cells transduced with Cdx2 acquired serial replating activity, were able to be continuously propagated in liquid culture, generated fully penetrant and transplantable AML in BM transplant recipients, and displayed dysregulated expression of Hox family members in vitro and in vivo. These results demonstrate that aberrant expression of the developmental regulatory gene CDX2 in the adult hematopoietic compartment is a frequent event in the pathogenesis of AML; suggest a role for CDX2 as part of a common effector pathway that promotes the proliferative capacity and self-renewal potential of myeloid progenitor cells; and support the hypothesis that CDX2 is responsible, in part, for the altered HOX gene expression that is observed in most cases of AML