Chromatin and DNA methylation dynamics during retinoic acid-induced RET gene transcriptional activation in neuroblastoma cells

Although it is well known that RET gene is strongly activated by retinoic acid (RA) in neuroblastoma cells, the mechanisms underlying such activation are still poorly understood. Here we show that a complex series of molecular events, that include modifications of both chromatin and DNA methylation state, accompany RA-mediated RET activation. Our results indicate that the primary epigenetic determinants of RA-induced RET activation differ between enhancer and promoter regions. At promoter region, the main mark of RET activation was the increase of H3K4me3 levels while no significant changes of the methylation state of H3K27 and H3K9 were observed. At RET enhancer region a bipartite chromatin domain was detected in unstimulated cells and a prompt demethylation of H3K27me3 marked RET gene activation upon RA exposure. Moreover, ChIP experiments demonstrated that EZH2 and MeCP2 repressor complexes were associated to the heavily methylated enhancer region in the absence of RA while both complexes were displaced during RA stimulation. Finally, our data show that a demethylation of a specific CpG site at the enhancer region could favor the displacement of MeCP2 from the heavily methylated RET enhancer region providing a novel potential mechanism for transcriptional regulation of methylated RA-regulated loci

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Innovative public and private measures to encourage the adoption of ecological practices and enhance the performance and sustainability of ecological agriculture

This deliverable presents the results of the research carried out in WP6 task 6.2 of the LIFT project, on the impact of policies on the adoption of ecological approaches and on the performance and sustainability of ecological agriculture. &nbsp;We first provide a short synthesis of the policy implications of the studies carried out in WP2, WP3 and WP4 of the LIFT project. These studies highlight some drawbacks of currently implemented schemes, such as the current Common Agricultural Policy (CAP) first and second pillar subsidies that may not be adequate for extensive technologies. In addition, these studies advocate policy compensation schemes that take into consideration the income forgone, given the regional potential, both in terms of agricultural production and environmental endowments. We then focus on the effect of Payments for Environmental Services (PES) using meta-analysis and quasi-experimental methods for about 150 PES-schemes implemented worldwide. We find that the effect of PES largely depends on their characteristics. Among others, eligibility of Ecosystem Services (ES) providers, contract length, reference design, payment constraint, monitoring system and the implementation zone of the PES schemes appear to be correlated with the probability of achieving positive environmental results. Nevertheless, the effectiveness of the PES-schemes investigated in this meta-analysis is shown to especially depend on the monitoring system implemented to ensure compliance and on the eligibility of ES providers. Using econometric analysis on French farm data, we also find that farmers&rsquo; incomes are not affected by their ecological practices, once the extra cost of these practices has been covered by the Agri-Environmental Schemes (AES) payment or promote some efficiency gains. The real cost of the transition is therefore on average well compensated by these payments. It does not imply that farms earn extra profit, and thus appears to respect World Trade Organisation (WTO) rules.</p