The YEASTRACT database: an upgraded information system for the analysis of gene and genomic transcription regulation in<i>Saccharomyces cerevisiae</i>

Teixeira, Miguel C.; Monteiro, Pedro T.; Guerreiro, Joana F.; Gonçalves, Joana P.; Mira, Nuno P.; Santos, Sandra C. dos; Cabrito, Tânia R.; Palma, Margarida; Costa, Catarina; Francisco, Alexandre P.; Madeira, Sara C.; Oliveira, Arlindo L.; Freitas, Ana T.; Sá‐Correia, Isabel

doi:10.1093/nar/gkt1015

Cited by 218 publications

(221 citation statements)

References 15 publications

Supporting

Mentioning

218

Contrasting

Order By: Relevance

“…Binding site density was estimated using the FIMO motif finding package using the default parameters (60). Binding site motifs for each transcription factor were taken from the Yeastract database (61). Transcription factor binding site density was estimated using a kernel density estimate with a 0.01 bandwidth.…”

Section: Methodsmentioning

confidence: 99%

Form and function of topologically associating genomic domains in budding yeast

Eser

Chandler-Brown

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The genome of metazoan cells is organized into topologically associating domains (TADs) that have similar histone modifications, transcription level, and DNA replication timing. Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity. Furthermore, these boundaries separate regions of similarly timed replication origins connecting the longknown effect of genomic context on replication timing to genome architecture. To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing. Forkhead factors do not regulate TAD formation, but do promote longer-range genomic interactions and control interactions between origins near the centromere. Thus, our work defines spatial organization within the budding yeast nucleus, demonstrates the conserved role of genome architecture in regulating DNA replication, and identifies a molecular mechanism specifically regulating interactions between pericentric origins. A n important distinction between eukaryotic and prokaryotic cells is the presence of the eukaryotic nucleus, which compartmentalizes the cell. It is becoming increasingly clear that the eukaryotic nuclear compartment contains additional layers of spatial organization, including the nucleolus, splicing bodies, transcriptional foci, and the peripheral localization of telomeres (1, 2). In addition, high-throughput chromosome conformation capture (Hi-C) technologies have recently revealed the spatial organization of chromatin into topologically associating domains (TADs) on the 100-kb to 1-Mb scale for mammals (3, 4), as well as the fly Drosophila melanogaster (5), the worm Caenorhabditis elegans (6), and the fission yeast Schizosaccharomyces pombe (7). Loci within a TAD are much more likely to interact with one another than with loci outside the domain (5,8,9).In metazoans, topological domains play important roles in coordinating the DNA-templated processes of replication and transcription (10-12). Chromatin within a TAD tends to have similar histone modifications, and consequently euchromatic or heterochromatic state, so that the genome is organized into self-associated globules that are either permissive or repressive of transcription. Repressive TADs are likely to be associated with the nuclear periphery (8). In addition to coordinating transcription, TADs also coordinate replication so that replication origins within a domain activate synchronously.That TAD nuclear organization is important for transcription and replication has motivated much recent work on the molecular mechanisms underlying TAD formation. The...

show abstract

Section: Methodsmentioning

confidence: 99%

Form and function of topologically associating genomic domains in budding yeast

Eser

Chandler-Brown

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Studies showing combinatorial control by Cbf1 and Met31/32 of Met4-dependent genes failed to identify by standard motif-finding approaches the Cbf1-binding site that we identified in the SUL1 promoter Carrillo et al 2012), although combinatorial regulation of SUL1 can be parsed by analyzing transcription after inducing or repressing sulfate-metabolism regulators Petti et al 2012). We searched the SUL1 promoter sequence using two yeast transcription factor databases, YEASTRACT (Teixeira et al 2006;Monteiro et al 2008;Abdulrehman et al 2011;Teixeira et al 2014) and YeTFaSCo (de Boer and Hughes 2012), to compare our results to the results from in silico analyses. Our search yielded 99 possible motifs, only one of which, a Met31 motif centered at 2410 (overlapping a site that we hypothesize to be a Met32 site), aligned with any of our predictions.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the SUL1 Promoter of Saccharomyces cerevisiae

et al. 2016

View full text Add to dashboard Cite

In the yeast Saccharomyces cerevisiae, beneficial mutations selected during sulfate-limited growth are typically amplifications of the SUL1 gene, which encodes the high-affinity sulfate transporter, resulting in fitness increases of .35% . Cis-regulatory mutations have not been observed at this locus; however, it is not clear whether this absence is due to a low mutation rate such that these mutations do not arise, or they arise but have limited fitness effects relative to those of amplification. To address this question directly, we assayed the fitness effects of nearly all possible point mutations in a 493-base segment of the gene's promoter through mutagenesis and selection. While most mutations were either neutral or detrimental during sulfate-limited growth, eight mutations increased fitness .5% and as much as 9.4%. Combinations of these beneficial mutations increased fitness only up to 11%. Thus, in the case of SUL1, promoter mutations could not induce a fitness increase similar to that of gene amplification. Using these data, we identified functionally important regions of the SUL1 promoter and analyzed three sites that correspond to potential binding sites for the transcription factors Met32 and Cbf1. Mutations that create new Met32-or Cbf1-binding sites also increased fitness. Some mutations in the untranslated region of the SUL1 transcript decreased fitness, likely due to the formation of inhibitory upstream open reading frames. Our methodology-saturation mutagenesis, chemostat selection, and DNA sequencing to track variants-should be a broadly applicable approach.KEYWORDS high-throughput sequencing; transcription; promoter mutagenesis; gene amplification; chemostat; yeast; Saccharomyces cerevisiae C HANGES in the extent or timing of gene expression can have profound effects on molecular and organismal phenotypes and thereby drive evolution (King and Wilson 1975;Wray 2007). Heritable noncoding variation can alter gene expression in cis or in trans (Skelly et al. 2009), and both have been shown to contribute significantly to gene expression variation (Ronald et al. 2005;Tirosh et al. 2009;Skelly et al. 2011). Two primary mechanisms by which cis variation can increase gene expression are increases in gene copy number and point mutations in regulatory regions. However, the relative effect size of amplification compared to point mutation is not known.It has been proposed that amplification is both quickly achieved and then reverts after fixation of fitness-increasing point mutations (Hendrickson et al. 2002;Yona et al. 2012). This mechanism raises the question of whether amplification is simply a transitional state that provides an increased chance for a beneficial point mutation to occur. Alternatively, gene amplification may be so frequently observed because the fitness effects it confers are greater than those achievable by point mutations. Gene amplifications have been found to be advantageous in many contexts, including phenotypic evolution (Hoekstra and Coyne 2007;Stern and Orgogozo 2008) an...

show abstract

“…The Gene Ontology category enrichment analyses were performed using FUNSPEC with default parameters (cutoff P value ϭ 0.01 and no Bonferroni correction) (28). The enrichments in specific transcription factortarget gene regulatory interactions were measured using the "rank TF" tool of YEASTRACT with default parameters (29).…”

Section: Methodsmentioning

confidence: 99%

Control of Plasma Membrane Permeability by ABC Transporters

et al. 2015

View full text Add to dashboard Cite

h ATP-binding cassette transporters Pdr5 and Yor1 from Saccharomyces cerevisiae control the asymmetric distribution of phospholipids across the plasma membrane as well as serving as ATP-dependent drug efflux pumps. Mutant strains lacking these transporter proteins were found to exhibit very different resistance phenotypes to two inhibitors of sphingolipid biosynthesis that act either late (aureobasidin A [AbA]) or early (myriocin [Myr]) in the pathway leading to production of these important plasma membrane lipids. These pdr5⌬ yor1 strains were highly AbA resistant but extremely sensitive to Myr. We provide evidence that these phenotypic changes are likely due to modulation of the plasma membrane flippase complexes, Dnf1/Lem3 and Dnf2/Lem3. Flippases act to move phospholipids from the outer to the inner leaflet of the plasma membrane. Genetic analyses indicate that lem3⌬ mutant strains are highly AbA sensitive and Myr resistant. These phenotypes are fully epistatic to those seen in pdr5⌬ yor1 strains. Direct analysis of AbA-induced signaling demonstrated that loss of Pdr5 and Yor1 inhibited the AbA-triggered phosphorylation of the AGC kinase Ypk1 and its substrate Orm1. Microarray experiments found that a pdr5⌬ yor1 strain induced a Pdr1-dependent induction of the entire Pdr regulon. Our data support the view that Pdr5/Yor1 negatively regulate flippase function and activity of the nuclear Pdr1 transcription factor. Together, these data argue that the interaction of the ABC transporters Pdr5 and Yor1 with the Lem3-dependent flippases regulates permeability of AbA via control of plasma membrane protein function as seen for the high-affinity tryptophan permease Tat2.

show abstract

The YEASTRACT database: an upgraded information system for the analysis of gene and genomic transcription regulation inSaccharomyces cerevisiae

Cited by 218 publications

References 15 publications

Form and function of topologically associating genomic domains in budding yeast

Form and function of topologically associating genomic domains in budding yeast

Comprehensive Analysis of the SUL1 Promoter of Saccharomyces cerevisiae

Control of Plasma Membrane Permeability by ABC Transporters

Contact Info

Product

Resources

About