arXiv subjects

Ferdinando Di Cunto

Publications and source records attributed to Ferdinando Di Cunto.

4 recordsLinked to original sources

arXiv2015

Quantitative study of crossregulation, noise and synchronization between microRNA targets in single cells

Recent studies reported complex post-transcriptional interplay among targets of a common pool of microRNAs, a class of small non-coding downregulators of gene expression. Behaving as microRNA-sponges, distinct RNA species may compete for binding to microRNAs and coregulate each other in a dose-dependent manner. Although previous studies in cell populations showed competition in vitro, the detailed dynamical aspects of this process, most importantly in physiological conditions, remains unclear. We address this point by monitoring protein expression of two targets of a common miRNA with quantitative single-cell measurements. In agreement with a detailed stochastic model of molecular titration, we observed that: (i) crosstalk between targets is possible only in particular stoichiometric conditions, (ii) a trade-off on the number of microRNA regulatory elements may induce the coexistence of two distinct cell populations, (iii) strong inter-targets correlations can be observed. This phenomenology is compatible with a small amount of mRNA target molecules per cell of the order of 10-100.

q-bio.MN↗

arXiv2007

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.

q-bio.GN↗

arXiv2005

Ab initio identification of putative human transcription factor binding sites by comparative genomics

We discuss a simple and powerful approach for the ab initio identification of cis-regulatory motifs involved in transcriptional regulation. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome. By using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence) in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites.

q-bio.GN↗

arXiv2005

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.

q-bio.GN↗