Inferring the transcriptional regulatory mechanism of signal-dependent gene expression via an integrative computational approach.

Eukaryotic transcription factors (TFs) coordinate different upstream signals to regulate the expression of their target genes. To unveil this regulatory network in B-cell receptor signaling, we developed a computational pipeline to systematically analyze the extracellular signal-regulated kinase (ERK)- and IκB kinase (IKK)-dependent transcriptome responses. We combined a bilinear regression method and kinetic modeling to identify the signal-to-TF and TF-to-gene dynamics, respectively. We input a set of time-course experimental data for B cells and concentrated on transcriptional activators. The results show that the combination of TFs differentially controlled by ERK and IKK could contribute divergent expression dynamics in orchestrating the B-cell response. Our findings provide insights into the regulatory mechanisms underlying signal-dependent gene expression in eukaryotic cells.

Analysis of the association between transcription factor binding site variants and distinct accompanying regulatory motifs in yeast.

It is generally accepted that genes are regulated by the interactions between transcription factors (TFs) and their binding sites (TFBSs). Some studies have demonstrated that nucleotide variants at variable positions in TFBSs affect yeast gene regulation. Furthermore, variable positions in TFBSs in association with distinct accompanying regulatory motifs of other TFs (i.e., co-TFs) can also impact gene regulation in eukaryotes. Given that, even low-affinity TF-DNA interactions are abundant in vivo; we used both low- and high-affinity TFBSs and performed a genome-wide analysis of associations between variable positions and co-TFs. We found that, in Saccharomyces cerevisiae, approximately 14% of the variable positions in TFBSs demonstrate such associations. These associations occurred in close proximity on the same promoters (i.e., highly co-localized). Moreover, such associations were highly conserved between sensu stricto yeasts and also influenced gene expression, which were consistent with enriched functional categories.

MetaABC--an integrated metagenomics platform for data adjustment, binning and clustering.

SUMMARY: MetaABC is a metagenomic platform that integrates several binning tools coupled with methods for removing artifacts, analyzing unassigned reads and controlling sampling biases. It allows users to arrive at a better interpretation via series of distinct combinations of analysis tools. After execution, MetaABC provides outputs in various visual formats such as tables, pie and bar charts as well as clustering result diagrams. AVAILABILITY: MetaABC source code and documentation are available at http://bits2.iis.sinica.edu.tw/MetaABC/ CONTACT: dywang@gate.sinica.edu.tw; hktsai@iis.sinica.edu.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Impact of DNA-binding position variants on yeast gene expression.

Transcription factors (TFs) regulate gene expression by binding to specific binding sites (TFBSs) in gene promoters. TFBS motifs may contain one or more variable positions. Although the prevailing assumption is that nucleotide variants at such positions are functionally equivalent, there is increasing evidence that such variants play a role in regulation of gene expression. In this article, we propose a method for studying the relationship between the expression of target genes and nucleotide variants in TFBS motifs at a genome-wide scale in Saccharomyces cerevisiae, especially the combinatorial effects of variants at two positions. Our analysis shows that nucleotide variations in more than one-third of variable positions and in 20% of dependent position pairs are highly correlated to gene expression. We define such positions as 'functional'. However, some positions are only functional as dependent pairs, but not individually. In addition, a significant proportion of the functional positions have been well conserved across all yeast-related species studied. We also find that some positions require the presence of co-occurring TFs, while others maintain their functionality in the absence of a co-occurring TF. Our analysis supports the importance of nucleotide variants at variable positions of TFBSs in gene regulation.