Correlating overrepresented upstream motifs to gene expression: a computational approach to regulatory element discovery in eukaryotes

Gene regulation in eukaryotes is mainly effected through transcription factors binding to rather short recognition motifs generally located upstream of the coding region. We present a novel computational method to identify regulatory elements in the upstream region of eukaryotic genes. The genes are grouped in sets sharing an overrepresented short motif in their upstream sequence. For each set, the average expression level from a microarray experiment is determined: If this level is significantly higher or lower than the average taken over the whole genome, then the overerpresented motif shared by the genes in the set is likely to play a role in their regulation. The method was tested by applying it to the genome of Saccharomyces cerevisiae, using the publicly available results of a DNA microarray experiment, in which expression levels for virtually all the genes were measured during the diauxic shift from fermentation to respiration. Several known motifs were correctly identified, and a new candidate regulatory sequence was determined.Comment: Published version available from http://www.biomedcentral.com/1471-2105/3/

Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions

3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years. We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs. Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification.Comment: Added two reference

Continuity of the visibility function

G. Beer defined the visibility function of a set S and proved its continuity in the interior of S. It is proved here that the visibility function of a planar Jordan domain S is continuous precisely at the cone points of the boundary of S

Computational identification of transcription factor binding sites by functional analysis of sets of genes sharing overrepresented upstream motifs

BACKGROUND: Transcriptional regulation is a key mechanism in the functioning of the cell, and is mostly effected through transcription factors binding to specific recognition motifs located upstream of the coding region of the regulated gene. The computational identification of such motifs is made easier by the fact that they often appear several times in the upstream region of the regulated genes, so that the number of occurrences of relevant motifs is often significantly larger than expected by pure chance. RESULTS: To exploit this fact, we construct sets of genes characterized by the statistical overrepresentation of a certain motif in their upstream regions. Then we study the functional characterization of these sets by analyzing their annotation to Gene Ontology terms. For the sets showing a statistically significant specific functional characterization, we conjecture that the upstream motif characterizing the set is a binding site for a transcription factor involved in the regulation of the genes in the set. CONCLUSIONS: The method we propose is able to identify many known binding sites in S. cerevisiae and new candidate targets of regulation by known transcription factors. Its application to less well studied organisms is likely to be valuable in the exploration of their regulatory interaction network.Comment: 19 pages, 1 figure. Published version with several improvements. Supplementary material available from the author

Modelling element distributions in the atmospheres of magnetic Ap stars

In recent papers convincing evidence has been presented for chemical stratification in Ap star atmospheres, and surface abundance maps have been shown to correlate with the magnetic field direction. Radiatively driven diffusion in magnetic fields is among the processes responsible for these inhomogeneities. Here we explore the hypothesis that equilibrium stratifications can, in a number of cases, explain the observed abundance maps and vertical distributions of the various elements. The investigation of equilibrium stratifications in stellar atmospheres with temperatures from 8500K to 12000K and fields up to 10 kG reveals considerable variations in the vertical distribution of the 5 elements studied (Mg, Si, Ca, Ti, Fe), often with zones of large over- or under-abundances and with indications of other competing processes (such as mass loss). Horizontal magnetic fields can be very efficient in helping the accumulation of elements in higher layers. A comparison between our calculations and the vertical abundance profiles and surface maps derived by magnetic Doppler imaging reveals that equilibrium stratifications are in a number of cases consistent with the main trends inferred from observed spectra. However, it is not clear whether such equilibrium solutions will ever be reached during the evolution of an Ap star.Comment: 7 pages, 6 figures, the paper will be published in Astronomy & Astrophysics, on November 200

The collagen chaperone HSP47 is a new interactor of APP that affects the levels of extracellular beta-amyloid peptides.

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Ab peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Ab peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques.The first is project n. A134, funded under the call ‘‘Bando Regionale sulla Ricerca Scientifica Applicata – 2004’’. The second is the DRUIDI (DRUg development In DIsease) project, funded under the call ‘‘Piattaforme Tecnologiche Innovative – 2008’’. The funder (Piedmont Region) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe

Relativistic fine structure oscillator strengths for Li-like ions: C IV - Si XII, S XIV, Ar XVI, Ca XVIII, Ti XX, Cr XXII, and Ni XXVI

Ab initio calculations including relativistic effects employing the Breit-Pauli R-matrix (BPRM) method are reported for fine structure energy levels and oscillator strengths upto n = 10 and 0.leq. l .leq.9 for 15 Li-like ions: C IV, N V, O VI, F VII, Ne VIII, Na IX, Mg X, Al XI, Si XII, S XIV, Ar XVI, Ca XIII, Ti XX, Cr XXII, and Ni XXVI. About one hundred bound fine structure energy levels of total angular momenta, 1/2 .leq. J .leq. 17/2 of even and odd parities, total orbital angular momentum, 0 .leq L .leq. 9 and spin multiplicity (2S+1) = 2, 4 are considered for each ion. The levels provide almost 900 dipole allowed and intercombination bound-bound transitions. The BPRM method enables consideration of large set of transitions with uniform accuracy compared to the best available theoretical methods. The CC eigenfunction expansion for each ion includes the lowest 17 fine structure energy levels of the core configurations 1s^2, 1s2s, 1s2p, 1s3s, 1s3p, and 1s3d. The calculated energies of the ions agree with the measured values to within 1% for most levels. The transition probabilities show good agreement with the best available calculated values. The results provide the largest sets of energy levels and transition rates for the ions and are expected to be useful in the analysis of X-ray and EUV spectra from astrophysical sources.Comment: 16 pgs., to appear in Astronomy and Astrophysic

Theoretical He I Emissivities in the Case B Approximation

We calculate the He I case B recombination cascade spectrum using improved radiative and collisional data. We present new emissivities over a range of electron temperatures and densities. The differences between our results and the current standard are large enough to have a significant effect not only on the interpretation of observed spectra of a wide variety of objects but also on determinations of the primordial helium abundance.Comment: Accepted to ApJ