SummaryIt is accepted that Saccharomyces cerevisiae genome arose from complete duplication of eight ancestral chromosomes; functionally normal ploidy was recovered because of the massive loss of 90% of duplicated genes. There is evidence that indicates that part of this selective conservation of gene pairs is compelling to yeast facultative metabolism. As an example, the duplicated NADP-glutamate dehydrogenase pathway has been maintained because of the differential expression of the paralogous GDH1 and GDH3 genes, and the biochemical specialization of the enzymes they encode. The present work has been aimed to the understanding of the regulatory mechanisms that modulate GDH3 transcriptional activation. Our results show that GDH3 expression is repressed in glucose-grown cultures, as opposed to what has been observed for GDH1 , and induced under respiratory conditions, or under stationary phase. Although GDH3 pertains to the nitrogen metabolic network, and its expression is Gln3p-regulated, complete derepression is ultimately determined by the carbon source through the action of the SAGA and SWI/SNF chromatin remodelling complexes. GDH3 carbonmediated regulation is over-imposed to that exerted by the nitrogen source, highlighting the fact that operation of facultative metabolism requires strict control of enzymes, like Gdh3p, involved in biosynthetic pathways that use tricarboxylic acid cycle intermediates.

In the face of changes in their environment, bacteria adjust gene expression levels and produce appropriate responses. The individual layers of this process have been widely studied: the transcriptional regulatory network describes the regulatory interactions that produce changes in the metabolic network, both of which are coordinated by the signaling network, but the interplay between them has never been described in a systematic fashion. Here, we formalize the process of detection and processing of environmental information mediated by individual transcription factors (TFs), utilizing a concept termed genetic sensory response units (GENSOR units), which are composed of four components: (1) a signal, (2) signal transduction, (3) genetic switch, and (4) a response. We used experimentally validated data sets from two databases to assemble a GENSOR unit for each of the 189 local TFs of Escherichia coli K-12 contained in the RegulonDB database. Further analysis suggested that feedback is a common occurrence in signal processing, and there is a gradient of functional complexity in the response mediated by each TF, as opposed to a one regulator/one pathway rule. Finally, we provide examples of other GENSOR unit applications, such as hypothesis generation, detailed description of cellular decision making, and elucidation of indirect regulatory mechanisms.

Cardiovascular disease (CVD) is a significant cause of morbidity and mortality across the world. A large proportion of CVD deaths are secondary to coronary artery disease (CAD) and myocardial infarction (MI). Even though prevention is the best strategy to reduce risk factors associated with MI, the use of cardioprotective interventions aimed at improving patient outcomes is of great interest. Opioid conditioning has been shown to be effective in reducing myocardial ischemia-reperfusion injury (IRI) and cardiomyocyte death. However, the molecular mechanisms behind these effects are under investigation and could provide the basis for the development of novel therapeutic approaches in the treatment of CVD. Non-coding RNAs (ncRNAs), which are functional RNA molecules that do not translate into proteins, are critical modulators of cardiac gene expression during heart development and disease. Moreover, ncRNAs such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are known to be induced by opioid receptor activation and regulate opioid signaling pathways. Recent advances in experimental and computational tools have accelerated the discovery and functional characterization of ncRNAs. In this study, we review the current understanding of the role of ncRNAs in opioid signaling and opioid-induced cardioprotection.

SummaryTranscription of an important number of divergent genes of Saccharomyces cerevisiae is controlled by intergenic regions, which constitute factual bidirectional promoters. However, few of such promoters have been characterized in detail. The analysis of the UGA3-GLT1 intergenic region has provided an interesting model to study the joint action of two global transcriptional activators that had been considered to act independently. Our results show that Gln3p and Gcn4p exert their effect upon cis -acting elements, which are shared in a bidirectional promoter. Accordingly, when yeast is grown on a low-quality nitrogen source, or under amino acid deprivation, the expression of both UGA3 and GLT1 is induced through the action of both these global transcriptional modulators that bind to a region of the bidirectional promoter. In addition, we demonstrate that chromatin organization plays a major role in the bidirectional properties of the UGA3-GLT1 promoter, through the action of an upstream Abf1p-binding consensus sequence and a polydAdT tract . Mutations in these cis -elements differentially affect transcription of UGA3 and GLT1 , and thus alter the overall relative expression. This is the first example of an intergenic region constituting a promoter whose bidirectional character is determined by chromatin organization.