Origin and diversification of the basic helix-loop-helix gene family in metazoans: insights from comparative genomics

BACKGROUND: Molecular and genetic analyses conducted in model organisms such as Drosophila and vertebrates, have provided a wealth of information about how networks of transcription factors control the proper development of these species. Much less is known, however, about the evolutionary origin of these elaborated networks and their large-scale evolution. Here we report the first evolutionary analysis of a whole superfamily of transcription factors, the basic helix-loop-helix (bHLH) proteins, at the scale of the whole metazoan kingdom. RESULTS: We identified in silico the putative full complement of bHLH genes in the sequenced genomes of 12 different species representative of the main metazoan lineages, including three non-bilaterian metazoans, the cnidarians Nematostella vectensis and Hydra magnipapillata and the demosponge Amphimedon queenslandica. We have performed extensive phylogenetic analyses of the 695 identified bHLHs, which has allowed us to allocate most of these bHLHs to defined evolutionary conserved groups of orthology. CONCLUSION: Three main features in the history of the bHLH gene superfamily can be inferred from these analyses: (i) an initial diversification of the bHLHs has occurred in the pre-Cambrian, prior to metazoan cladogenesis; (ii) a second expansion of the bHLH superfamily occurred early in metazoan evolution before bilaterians and cnidarians diverged; and (iii) the bHLH complement during the evolution of the bilaterians has been remarkably stable. We suggest that these features may be extended to other developmental gene families and reflect a general trend in the evolution of the developmental gene repertoires of metazoans

methBLAST and methPrimerDB: web-tools for PCR based methylation analysis

BACKGROUND: DNA methylation plays an important role in development and tumorigenesis by epigenetic modification and silencing of critical genes. The development of PCR-based methylation assays on bisulphite modified DNA heralded a breakthrough in speed and sensitivity for gene methylation analysis. Despite this technological advancement, these approaches require a cumbersome gene by gene primer design and experimental validation. Bisulphite DNA modification results in sequence alterations (all unmethylated cytosines are converted into uracils) and a general sequence complexity reduction as cytosines become underrepresented. Consequently, standard BLAST sequence homology searches cannot be applied to search for specific methylation primers. RESULTS: To address this problem we developed methBLAST, a sequence similarity search program, based on the original BLAST algorithm but querying in silico bisulphite modified genome sequences to evaluate oligonucleotide sequence similarities. Apart from the primer specificity analysis tool, we have also developed a public database termed methPrimerDB for the storage and retrieval of validated PCR based methylation assays. The web interface allows free public access to perform methBLAST searches or database queries and to submit user based information. Database records can be searched by gene symbol, nucleotide sequence, analytical method used, Entrez Gene or methPrimerDB identifier, and submitter's name. Each record contains a link to Entrez Gene and PubMed to retrieve additional information on the gene, its genomic context and the article in which the methylation assay was described. To assure and maintain data integrity and accuracy, the database is linked to other reference databases. Currently, the database contains primer records for the most popular PCR-based methylation analysis methods to study human, mouse and rat epigenetic modifications. methPrimerDB and methBLAST are available at and . CONCLUSION: We have developed two integrated and freely available web-tools for PCR based methylation analysis. methBLAST allows in silico assessment of primer specificity in PCR based methylation assays that can be stored in the methPrimerDB database, which provides a search portal for validated methylation assays

Dimension rigidity in conformal structures

Let $\Lambda$ be the limit set of a conformal dynamical system, i.e. a Kleinian group acting on either finite- or infinite-dimensional real Hilbert space, a conformal iterated function system, or a rational function. We give an easily expressible sufficient condition, requiring that the limit set is not too much bigger than the radial limit set, for the following dichotomy: $\Lambda$ is either a real-analytic manifold or a fractal in the sense of Mandelbrot (i.e. its Hausdorff dimension is strictly greater than its topological dimension). Our primary focus is on the infinite-dimensional case. An important component of the strategy of our proof comes from the rectifiability techniques of Mayer and Urba\'nski ('03), who obtained a dimension rigidity result for conformal iterated function systems (including those with infinite alphabets). In order to handle the infinite dimensional case, both for Kleinian groups and for iterated function systems, we introduce the notion of pseudorectifiability, a variant of rectifiability, and develop a theory around this notion similar to the theory of rectifiable sets. Our approach also extends existing results in the finite-dimensional case, where it unifies the realms of Kleinian groups, conformal iterated function systems, and rational functions. For Kleinian groups, we improve on the rigidity result of Kapovich ('09) by substantially weakening its hypothesis of geometrical finiteness. Moreover, our proof, based on rectifiability, is entirely different than that of Kapovich, which depends on homological algebra. Another advantage of our approach is that it allows us to use the "demension" of \v{S}tan$'$ko ('69) as a substitute for topological dimension. For example, we prove that any dynamically defined version of Antoine's necklace must have Hausdorff dimension strictly greater than 1 (i.e. the demension of Antoine's necklace)

Definitions of quasiconformality

We establish that the infinitesimal “ H -definition” for quasiconformal mappings on Carnot groups implies global quasisymmetry, and hence the absolute continuity on almost all lines. Our method is new even in R n where we obtain that the “limsup” condition in the H -definition can be replaced by a “liminf” condition. This leads to a new removability result for (quasi)conformal mappings in Euclidean spaces. An application to parametrizations of chord-arc surfaces is also given.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46582/1/222_2005_Article_BF01241122.pd

Etude moléculaire des gènes UGA35 et UGA43 codant des facteurs de régulation transcriptionnelle communs aux voies cataboliques du gama-aminobutyrate (GABA) et de l'urée chez Saccharomyces cerevisiae

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Etude moléculaire des gènes UGA35 et UGA43 codant des facteurs de régulation transcriptionnelle communs aux voies cataboliques du gama-aminobutyrate (GABA) et de l'urée chez Saccharomyces cerevisiae

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

The pleiotropic UGA35(DURL) regulatory gene of Saccharomyces cerevisiae: cloning, sequence and identity with the DAL81 gene.

The UGA35 gene of Saccharomyces cerevisiae (also called DURL) encodes a positive regulator of the expression of structural genes involved in 4-aminobutyric acid (GABA) and urea catabolisms. The UGA35 gene has been cloned by complementation of function and identified by chromosomal gene replacement. The sequence of this regulatory gene and its flanking regions has been established. Our data reveal an open reading frame of 2892 nt, corresponding to 964 amino acids (aa). The deduced UGA35 aa sequence shares several similarities with that of other regulatory proteins, suggesting that the UGA35 gene encodes a DNA-binding transcriptional activator. We also show that UGA35 and the DAL81 regulatory gene controlling allantoin and urea catabolisms are one and the same gene. This means that the same factor is required for specific induction of three distinct catabolic pathways, namely those involved in GABA, urea and allantoin utilization as nitrogen sources.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Mutational and expression analysis of the UGA43 negative regulatory gene of Saccharomyces cerevisiae

info:eu-repo/semantics/publishe

The UGA43 negative regulatory gene of Saccharomyces cerevisiae contains both a GATA-1 type zinc finger and a putative leucine zipper.

The UGA43 gene of Saccharomyces cerevisiae is required for repression of inducible genes involved in the utilization of 4-aminobutyric acid (GABA) or urea as nitrogen sources. The UGA43 gene has been cloned by complementation of a uga43 mutation. The N-terminal region of the UGA43 protein is very similar to the DNA-binding zinc-finger region typical of the GATA regulatory factor family in vertebrates. UGA43 is the first reported instance of a GATA protein with a negative regulatory function. The C-terminal region of the predicted UGA43 protein contains a putative leucine zipper. Sequencing of three uga43 mutant alleles suggests that the GATA and putative leucine-zipper regions are both required for the repressive activity of UGA43. UGA43 appears to be a highly regulated gene. On "poor" nitrogen sources, UGA43 transcripts are measured at high levels whereas they are nearly undetectable in conditions of nitrogen catabolite repression. The levels measured on "poor" nitrogen sources are further increased in uga43 mutant cells, suggesting that UGA43 exerts negative autoregulation.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe