Mapping Yeast Transcriptional Networks

Abstract

The term “transcriptional network” refers to the mechanism(s) that underlies coordinated expression of genes, typically involving transcription factors (TFs) binding to the promoters of multiple genes, and individual genes controlled by multiple TFs. A multitude of studies in the last two decades have aimed to map and characterize transcriptional networks in the yeast Saccharomyces cerevisiae. We review the methodologies and accomplishments of these studies, as well as challenges we now face. For most yeast TFs, data have been collected on their sequence preferences, in vivo promoter occupancy, and gene expression profiles in deletion mutants. These systematic studies have led to the identification of new regulators of numerous cellular functions and shed light on the overall organization of yeast gene regulation. However, many yeast TFs appear to be inactive under standard laboratory growth conditions, and many of the available data were collected using techniques that have since been improved. Perhaps as a consequence, comprehensive and accurate mapping among TF sequence preferences, promoter binding, and gene expression remains an open challenge. We propose that the time is ripe for renewed systematic efforts toward a complete mapping of yeast transcriptional regulatory mechanisms.

High-Resolution Global Analysis of the Influences of Bas1 and Ino4 Transcription Factors on Meiotic DNA Break Distributions in Saccharomyces cerevisiae

“…Moreover, only a minority fraction of the hotspots that changed in the TF mutants were detectably bound by Bas1 or Ino4 protein during meiosis. This modest correspondence between TF binding and DSB activity is analogous to the relation of TFs to transcriptional regulation: numerous studies have documented that only a small fraction of genes whose promoters are bound by a given TF show expression changes when the TF is deleted, and only a small fraction of the genes that change expression are direct binding targets (reviewed in MacQuarrie et al 2011;Hughes and De Boer 2013). Although it is possible that the ChIP-seq failed to detect direct Bas1 or Ino4 binding that does in fact occur, the results strongly indicate that a substantial portion of the DSB-modulating activity of these TFs is indirect.…”

Genome-wide determinants of sequence-specific DNA binding of general regulatory factors

“…To study the DNA shape aspects of Mcm1 binding, we analyzed a subset of bound and unbound motif occurrences from Supplemental Figure S7A that contained all of the most highly conserved nucleotides of the 16-bp pseudosymmetric motif (TTnCCnnnTnnGGnAA) (Fig. 4A,B; Shore and Sharrocks 1995;Hughes and de Boer 2013). DNA shape analysis of these motifs revealed an intrinsically negative roll at the motif midpoint (Fig.…”

“…Rap1 is another GRF that organizes chromatin, binds promoters of genes that encode ribosomal and glycolytic proteins, and binds telomeres (Shore 1994;Ganapathi et al 2011;Hughes and de Boer 2013). When the core DNA sequence of the Rap1 motif (Fig.…”

“…These factors (Reb1, Abf1, Mcm1, Rap1, and Cbf1) organize nucleosomes and are referred to as general regulatory factors (GRFs) (Yu and Morse 1999;Yarragudi et al 2004;Raisner et al 2005;Badis et al 2008;Hartley and Madhani 2009;Hughes and de Boer 2013). By directing nucleosome organization, GRFs help maintain nucleosomefree promoter regions (NFRs) (Badis et al 2008;Hartley and Madhani 2009), thereby giving the transcription machinery access to the DNA.…”

Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in Arabidopsis

“…For example, dynamic GRN studies in plants have uncovered genome-wide responses that occur within as little as 3 min following a nitrogen (N) nutrient signal perturbation (1). However, many of the underlying rapid and temporal network connections between transcription factors (TFs) and their targets elude detection even in fine-scale time-course studies (2,3), as current methods, such as chromatin immunoprecipitation (ChIP), require stable TF binding in at least one time point to identify primary targets (4)(5)(6). However, recent models suggest that GRNs built solely on TF binding data are insufficient to recapture transcriptional regulation (7)(8)(9).…”