title: The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis.
abstract: Asymmetric division during sporulation by Bacillus subtilis generates a mother cell that undergoes a 5-h program of differentiation. The program is governed by a hierarchical cascade consisting of the transcription factors: sigma(E), sigma(K), GerE, GerR, and SpoIIID. The program consists of the activation and repression of 383 genes. The sigma(E) factor turns on 262 genes, including those for GerR and SpoIIID. These DNA-binding proteins downregulate almost half of the genes in the sigma(E) regulon. In addition, SpoIIID turns on ten genes, including genes involved in the appearance of sigma(K). Next, sigma(K) activates 75 additional genes, including that for GerE. This DNA-binding protein, in turn, represses half of the genes that had been activated by sigma(K) while switching on a final set of 36 genes. Evidence is presented that repression and activation contribute to proper morphogenesis. The program of gene expression is driven forward by its hierarchical organization and by the repressive effects of the DNA-binding proteins. The logic of the program is that of a linked series of feed-forward loops, which generate successive pulses of gene transcription. Similar regulatory circuits could be a common feature of other systems of cellular differentiation.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Eichenberger
authors.forename: Masaya
authors.initials: M
authors.lastname: Fujita
authors.forename: Shane T
authors.initials: ST
authors.lastname: Jensen
authors.forename: Erin M
authors.initials: EM
authors.lastname: Conlon
authors.forename: David Z
authors.initials: DZ
authors.lastname: Rudner
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Wang
authors.forename: Caitlin
authors.initials: C
authors.lastname: Ferguson
authors.forename: Koki
authors.initials: K
authors.lastname: Haga
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.forename: Jun S
authors.initials: JS
authors.lastname: Liu
authors.forename: Richard
authors.initials: R
authors.lastname: Losick
mesh_terms: D020816:Amino Acid Motifs; D001412:Bacillus subtilis / Q000235:genetics* / Q000502:physiology*; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003850:Deoxyribonuclease I / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013171:Spores, Bacterial / Q000737:chemistry*; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C030069:spore-specific proteins, Bacillus; D004247:DNA; D003850:Deoxyribonuclease I; D001616:beta-Galactosidase