KOALAB: A new method for regulatory motif search. Illustration on alternative splicing regulation in HIV-1

Discovering heterogeneous regulatory motifs remains a difficult problem in biological sequence analysis. In this context, statistical learning or pattern search techniques on their own have shown some limitations. However, significant benefits can be taken from their complementarity. We selected two state-of-the-art methods: a multi-class support vector machine (M-SVM) from the statistical learning domain associated with a performant discrete pattern matching algorithm grappe, and in- tegrated them into a web technology based graphical software: KOALAB (KOupled Algorithmic and Learning Approach for Biology)1 . We applied our method on motif discovery within nucleic acid sequences using experimental SELEX results as training database for the M-SVM. An application dealing with the search for splicing regulatory protein binding sites in HIV-1 genome shows the potential of such an approach

Facteurs de transcription à motif bHLH, étude de leurs fonctions au cours de la neurogénèse et l'hématopoïèse précoces chez la Drosophile

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Two isoforms of Serpent containing either one or two GATA zinc fingers have different roles in Drosophila haematopoiesis

serpent (srp) encodes a GATA transcription factor essential for haematopoiesis in Drosophila. Previously, Srp was shown to contain a single GATA zinc finger of C-terminal type. Here we show that srp encodes different isoforms, generated by alternative splicing, that contain either only a C-finger (SrpC) or both a C- and an N-finger (SrpNC). The presence of the N-finger stabilizes the interaction of Srp with palindromic GATA sites and allows interaction with the Friend of GATA factor U-shaped (Ush). We have examined the respective functions of SrpC and SrpNC during embryonic haematopoiesis. Both isoforms individually rescue blood cell formation that is lacking in an srp null mutation. Interestingly, while SrpC and SrpNC activate some genes in a similar manner, they regulate others differently. Interaction between SrpNC and Ush is responsible for some but not all aspects of the distinct activities of SrpC and SrpNC. Our results suggest that the inclusion or exclusion of the N-finger in the naturally occurring isoforms of Srp can provide an effective means of extending the versatility of srp function during development

Fatal Cowpox Virus Infection in Human Fetus, France, 2017

International audienc

Organization and Evolution of a Gene-Rich Region of the Mouse Genome: A 12.7-Mb Region Deleted in the Del(13)Svea36H Mouse

Del(13)Svea36H (Del36H) is a deletion of ∼20% of mouse chromosome 13 showing conserved synteny with human chromosome 6p22.1-6p22.3/6p25. The human region is lost in some deletion syndromes and is the site of several disease loci. Heterozygous Del36H mice show numerous phenotypes and may model aspects of human genetic disease. We describe 12.7 Mb of finished, annotated sequence from Del36H. Del36H has a higher gene density than the draft mouse genome, reflecting high local densities of three gene families (vomeronasal receptors, serpins, and prolactins) which are greatly expanded relative to human. Transposable elements are concentrated near these gene families. We therefore suggest that their neighborhoods are gene factories, regions of frequent recombination in which gene duplication is more frequent. The gene families show different proportions of pseudogenes, likely reflecting different strengths of purifying selection and/or gene conversion. They are also associated with relatively low simple sequence concentrations, which vary across the region with a periodicity of ∼5 Mb. Del36H contains numerous evolutionarily conserved regions (ECRs). Many lie in noncoding regions, are detectable in species as distant as Ciona intestinalis, and therefore are candidate regulatory sequences. This analysis will facilitate functional genomic analysis of Del36H and provides insights into mouse genome evolution