PhD Public defense - Morgane Thomas-Chollier Title: "Evolutionary study of the Hox gene family with matrix-based bioinformatics approaches" joint PhD supervision between the Vrije Universiteit Brussel (Prof. L. Leyns - Laboratory of Cell Genetics) and the Université Libre de Bruxelles (Prof J. van Helden - Service de Bioinformatique des Génomes et des réseaux (BiGRe)) June 27, 2008, at 16:00 Vrije Universiteit Brussel - Campus Etterbeek Pleinlaan 2, 1050 Brussels Building D, room D2.01 « promotiezaal » Access : http://www.vub.ac.be/image/3brussel_large.jpg Hox genes belong to the family of homeobox transcription factors characterised by a 60 amino acids region called homeodomain. These genes are evolutionary conserved and play crucial roles in the development of animals. In vertebrates, this family of genes can be divided into 14 groups of homology. The first goal of this thesis was to design an automated approach to assign the growing number of Hox sequences into their groups of homology. The resulting program, HoxPred, classifies Hox sequences on the basis of their scores for a combination of protein generalised profiles. This program was applied to clarify the evolutionary history of the HoxC1a genes in teleost fish. As transcription factors, Hox proteins regulate target genes by specifically binding DNA on cis-regulatory elements. Only a few of these target genes have been identified so far. The second goal of this work was to evaluate whether it is possible to apply computational approaches to detect Hox cis-regulatory elements in genomic sequences. For this, we participated to the development of matrix-based pattern matching approaches in the Regulatory Sequence Analysis Tools. After having performed a statistical validation of the pattern-matching scores, we focused on a study case based on the vertebrate HoxB1 protein, which binds DNA with its cofactors Pbx and Meis. The study aimed at predicting combinations of cis-regulatory elements for these three transcription factors. Contact person : morgane@bigre.ulb.ac.be