P-Element Homing Is Facilitated by engrailed Polycomb-Group Response Elements in Drosophila melanogaster

P-element vectors are commonly used to make transgenic Drosophila and generally insert in the genome in a nonselective manner. However, when specific fragments of regulatory DNA from a few Drosophila genes are incorporated into P-transposons, they cause the vectors to be inserted near the gene from which the DNA fragment was derived. This is called P-element homing. We mapped the minimal DNA fragment that could mediate homing to the engrailed/invected region of the genome. A 1.6 kb fragment of engrailed regulatory DNA that contains two Polycomb-group response elements (PREs) was sufficient for homing. We made flies that contain a 1.5kb deletion of engrailed DNA (enΔ1.5) in situ, including the PREs and the majority of the fragment that mediates homing. Remarkably, homing still occurs onto the enΔ1. 5 chromosome. In addition to homing to en, P[en] inserts near Polycomb group target genes at an increased frequency compared to P[EPgy2], a vector used to generate 18,214 insertions for the Drosophila gene disruption project. We suggest that homing is mediated by interactions between multiple proteins bound to the homing fragment and proteins bound to multiple areas of the engrailed/invected chromatin domain. Chromatin structure may also play a role in homing

Genome-Wide Tissue-Specific Occupancy of the Hox Protein Ultrabithorax and Hox Cofactor Homothorax in Drosophila

The Hox genes are responsible for generating morphological diversity along the anterior-posterior axis during animal development. The Drosophila Hox gene Ultrabithorax (Ubx), for example, is required for specifying the identity of the third thoracic (T3) segment of the adult, which includes the dorsal haltere, an appendage required for flight, and the ventral T3 leg. Ubx mutants show homeotic transformations of the T3 leg towards the identity of the T2 leg and the haltere towards the wing. All Hox genes, including Ubx, encode homeodomain containing transcription factors, raising the question of what target genes Ubx regulates to generate these adult structures. To address this question, we carried out whole genome ChIP-chip studies to identify all of the Ubx bound regions in the haltere and T3 leg imaginal discs, which are the precursors to these adult structures. In addition, we used ChIP-chip to identify the sites bound by the Hox cofactor, Homothorax (Hth). In contrast to previous ChIP-chip studies carried out in Drosophila embryos, these binding studies reveal that there is a remarkable amount of tissue- and transcription factor-specific binding. Analyses of the putative target genes bound and regulated by these factors suggest that Ubx regulates many downstream transcription factors and developmental pathways in the haltere and T3 leg. Finally, we discovered additional DNA sequence motifs that in some cases are specific for individual data sets, arguing that Ubx and/or Hth work together with many regionally expressed transcription factors to execute their functions. Together, these data provide the first whole-genome analysis of the binding sites and target genes regulated by Ubx to specify the morphologies of the adult T3 segment of the fly

Fast Point Multiplication Algorithms for Binary Elliptic Curves with and without Precomputation

In this paper we introduce new methods for computing constant-time variable-base point multiplications over the Galbraith-Lin-Scott (GLS) and the Koblitz families of elliptic curves. Using a left-to-right double-and-add and a right-to-left halve-and-add Montgomery ladder over a GLS curve, we present some of the fastest timings yet reported in the literature for point multiplication. In addition, we combine these two procedures to compute a multi-core protected scalar multiplication. Furthermore, we designed for the first time a regular $\tau$-adic scalar expansion for Koblitz curves. As a result, using the regular recoding approach, we set the speed record for a single constant-time point multiplication on standardized binary elliptic curves at the $128$-bit security level

Avis en réponse à la saisine du 7 novembre 2013, de Madame Marie-Christine Blandin, relative à l’article de Snell et al. (Food and Chemical Toxicology, 2012)

Le Haut Conseil des biotechnologies (HCB) a été saisi le 7 novembre 2013 par Madame la Sénatrice Marie-Christine Blandin, en vertu de l’article L531-3 du code de l’environnement, d’une demande d’avis relative à l’article de Snell et al., intitulé «Assessment of the health impact of GM plant diets in long-term and multigenerational animal feeding trials: A literature review», publié dans la revue Food and Chemical Toxicology (Snellet al.,2012). Pour répondre aux questions de la saisine, le Comité Scientifique (CS) du HCB a constitué un groupe de travail ad hoc. A la suite du compte-rendu de ce dernier, le CS du HCB a procédé à l’examen du projet de réponse le 25 février 2014 sous la présidence de Jean-Christophe Pagès

Alternative Epigenetic Chromatin States of Polycomb Target Genes

Polycomb (PcG) regulation has been thought to produce stable long-term gene silencing. Genomic analyses in Drosophila and mammals, however, have shown that it targets many genes, which can switch state during development. Genetic evidence indicates that critical for the active state of PcG target genes are the histone methyltransferases Trithorax (TRX) and ASH1. Here we analyze the repertoire of alternative states in which PcG target genes are found in different Drosophila cell lines and the role of PcG proteins TRX and ASH1 in controlling these states. Using extensive genome-wide chromatin immunoprecipitation analysis, RNAi knockdowns, and quantitative RT-PCR, we show that, in addition to the known repressed state, PcG targets can reside in a transcriptionally active state characterized by formation of an extended domain enriched in ASH1, the N-terminal, but not C-terminal moiety of TRX and H3K27ac. ASH1/TRX N-ter domains and transcription are not incompatible with repressive marks, sometimes resulting in a "balanced" state modulated by both repressors and activators. Often however, loss of PcG repression results instead in a "void" state, lacking transcription, H3K27ac, or binding of TRX or ASH1. We conclude that PcG repression is dynamic, not static, and that the propensity of a target gene to switch states depends on relative levels of PcG, TRX, and activators. N-ter TRX plays a remarkable role that antagonizes PcG repression and preempts H3K27 methylation by acetylation. This role is distinct from that usually attributed to TRX/MLL proteins at the promoter. These results have important implications for Polycomb gene regulation, the "bivalent" chromatin state of embryonic stem cells, and gene expression in development

Avis en réponse à la saisine HCB - dossier C/NL/06/01_001. Paris, le 17 octobre 2018

Le Haut Conseil des biotechnologies (HCB) a été saisi le 14 août 2018 par les autorités compétentes françaises (le ministère de l’Agriculture et de l’Alimentation) d’une demande d’avis relative au dossier C/NL/06/01_001 de demande de renouvellement d’autorisation de mise sur le marché de la lignée d’oeillets génétiquement modifiés 123.8.12 (identificateur unique FLO- 40689-6) à des fins d’importation et de commercialisation de fleurs coupées. Ce dossier a été déposé par la société Suntory Flowers Limited auprès des autorités compétentes néerlandaises sur le fondement de la directive 2001/18/CE. Conformément à cette directive, la Commission européenne a adressé le rapport d’évaluation des Pays-Bas ainsi que le dossier du pétitionnaire à l’ensemble des Etats membres, qui disposent de 60 jours pour faire des commentaires, demander des informations complémentaires ou émettre des objections à la mise sur le marché. Par cette saisine, les autorités compétentes françaises consultent le HCB dans cette perspective, en amont du vote des Etats membres à la Commission européenne. Le Comité scientifique (CS)2 du HCB a examiné le dossier en séance du 17 octobre 2018 sous la présidence de Jean-Christophe Pagès. Le présent avis a été adopté en séance et publié le 23 octobre 2018