title: Target hub proteins serve as master regulators of development in yeast.
abstract: To understand the organization of the transcriptional networks that govern cell differentiation, we have investigated the transcriptional circuitry controlling pseudohyphal development in Saccharomyces cerevisiae. The binding targets of Ste12, Tec1, Sok2, Phd1, Mga1, and Flo8 were globally mapped across the yeast genome. The factors and their targets form a complex binding network, containing patterns characteristic of autoregulation, feedback and feed-forward loops, and cross-talk. Combinatorial binding to intergenic regions was commonly observed, which allowed for the identification of a novel binding association between Mga1 and Flo8, in which Mga1 requires Flo8 for binding to promoter regions. Further analysis of the network showed that the promoters of MGA1 and PHD1 were bound by all of the factors used in this study, identifying them as key target hubs. Overexpression of either of these two proteins specifically induced pseudohyphal growth under noninducing conditions, highlighting them as master regulators of the system. Our results indicate that target hubs can serve as master regulators whose activity is sufficient for the induction of complex developmental responses and therefore represent important regulatory nodes in biological networks.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Borneman
authors.forename: Justine A
authors.initials: JA
authors.lastname: Leigh-Bell
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Yu
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C100940:FLO8 protein, S cerevisaie; D009687:Nuclear Proteins; C085984:PHD1 protein, S cerevisiae; D012097:Repressor Proteins; C097076:SOK2 protein, S cerevisiae; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C069926:TEC1 protein, S cerevisiae; D015534:Trans-Activators; D014157:Transcription Factors