SUMMARY Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.

MotivationThe computational search for promoters in prokaryotes remains an attractive problem in bioinformatics. Despite the attention it has received for many years, the problem has not been addressed satisfactorily. In any bacterial genome, the transcription start site is chosen mostly by the sigma (σ) factor proteins, which control the gene activation. The majority of published bacterial promoter prediction tools target σ70 promoters in Escherichia coli. Moreover, no σ-specific classification of promoters is available for prokaryotes other than for E. coli.ResultsHere, we introduce bTSSfinder, a novel tool that predicts putative promoters for five classes of σ factors in Cyanobacteria (σA, σC, σH, σG and σF) and for five classes of sigma factors in E. coli (σ70, σ38, σ32, σ28 and σ24). Comparing to currently available tools, bTSSfinder achieves higher accuracy (MCC = 0.86, F1-score = 0.93) compared to the next best tool with MCC = 0.59, F1-score = 0.79) and covers multiple classes of promoters.Availability and ImplementationbTSSfinder is available standalone and online at http://www.cbrc.kaust.edu.sa/btssfinder.Supplementary information Supplementary data are available at Bioinformatics online.

Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.

We would like to correct the author list of the above paper as a number of contributors that were on the original submitted version of the manuscript were inadvertently removed in the revision process. We are sorry that we did not detect these omissions in our review of the galley proofs.