The Program of Gene Transcription for a Single Differentiating Cell Type during Sporulation in Bacillus subtilis

Eichenberger, Patrick; Fujita, Masaya; Jensen, Shane T.; Conlon, Erin M.; Rudner, David Z.; Wang, Stephanie T.; Ferguson, Caitlin C.; Haga, Koki; Sato, Tsutomu; Liu, Jun S.; Losick, Richard

doi:10.1371/journal.pbio.0020328

Cited by 327 publications

(467 citation statements)

References 106 publications

Supporting

Mentioning

434

Contrasting

Unclassified

Order By: Relevance

“…42 Feed-forward loops of this type are widespread regulatory elements and are implicated in sign-sensitive delay and preventing inactivation of the target gene program when input signals are lost (i.e., they serve as stabilizers of target gene expression) and have been shown to be relevant in the context of cellular differentiation. [42][43][44][45] Our analysis of Grhl2-deficient mice revealed that Grhl2 is required for nephric duct lumen expansion in vivo. Because globally Grhl2-deficient mice exhibit embryonic lethality at E11.5, 8 we were unable to analyze the role of Grhl2 in the ureteric bud or the collecting duct of the developing and mature kidney in this model.…”

Section: Discussionmentioning

confidence: 79%

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Aue

Hinze

Walentin

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Grainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcriptional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4, and Rab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrier formation in Grhl2-deficient collecting duct cells. Hence, we identified a Grhl2/Ovol2 network controlling Cldn4 and Rab25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia. The renal collecting duct's vital electrolyte and waterregulatory functions are carried out by highly specialized cell populations. 1 The collecting duct itself is composed of a tight epithelium, which separates the urinary compartment from a hypertonic interstitium and maintains a barrier to concentration gradients. The collecting duct derives from the ureteric bud, which emanates from the nephric duct and then undergoes branching morphogenesis in response to signals from the adjacent metanephric mesenchyme. 2 Many of the genes that are critical for aspects of nephric duct development continue to be expressed in the ureteric bud and collecting duct, serving roles in development, differentiation, and maintenance of these cells (e.g., Pax2/8, Gata3, Emx2, and Hnf1b). 3 Little is known about the molecular pathways governing the specific epithelial properties of these cells, although it is clear that these epithelia share several cell biologic properties such as a uniform tubular appearance characterized by a cuboidal epithelium surrounding a fluid-filled lumen and a molecular composition of the apical junctional complex that includes

show abstract

Section: Discussionmentioning

confidence: 79%

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Aue

Hinze

Walentin

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…This is another example of a cell cycle control circuit design feature that enhances robustness by preventing timing glitches (2). The regulatory configuration of CtrA and SciP and their coregulated genes fits the type-1 incoherent feedforward loop circuit motif that is found in many regulatory circuits, often in arrangements in which multiple functionally related genes are coordinately regulated (21)(22)(23). The type-1 incoherent feedforward loop motif is a regulatory configuration in which an activator (i.e., CtrA) controls a target gene (e.g., a flagellar gene) and also activates a repressor of that target gene (i.e., SciP).…”

Section: Discussionmentioning

confidence: 93%

An essential transcription factor, SciP, enhances robustness of Caulobacter cell cycle regulation

Tan

Kozdon

Shen

et al. 2010

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

118

View full text Add to dashboard Cite

A cyclical control circuit composed of four master regulators drives the Caulobacter cell cycle. We report that SciP, a helix-turn-helix transcription factor, is an essential component of this circuit. SciP is cell cycle-controlled and co-conserved with the global cell cycle regulator CtrA in the α-proteobacteria. SciP is expressed late in the cell cycle and accumulates preferentially in the daughter swarmer cell. At least 58 genes, including many flagellar and chemotaxis genes, are regulated by a type 1 incoherent feedforward motif in which CtrA activates sciP, followed by SciP repression of ctrA and CtrA target genes. We demonstrate that SciP binds to DNA at a motif distinct from the CtrA binding motif that is present in the promoters of genes co-regulated by SciP and CtrA. SciP overexpression disrupts the balance between activation and repression of the CtrASciP coregulated genes yielding filamentous cells and loss of viability. The type 1 incoherent feedforward circuit motif enhances the pulse-like expression of the downstream genes, and the negative feedback to ctrA expression reduces peak CtrA accumulation. The presence of SciP in the control network enhances the robustness of the cell cycle to varying growth rates.CtrA | feedback | genetic circuit

show abstract

“…The Spo0F protein has been identified in both Bacillus subtilis and B. anthracis as being involved in one of the early/intermediate phosphor-relay events that leads to sporulation (27) (Fig. 3), and mutants in spo0F have been generated that do not sporulate because of lack of signal (28,29).…”

Section: Discussionmentioning

confidence: 99%

Bacillus anthracis comparative genome analysis in support of the Amerithrax investigation

Rasko

Worsham

Abshire

et al. 2011

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

157

104

View full text Add to dashboard Cite

Before the anthrax letter attacks of 2001, the developing field of microbial forensics relied on microbial genotyping schemes based on a small portion of a genome sequence. Amerithrax, the investigation into the anthrax letter attacks, applied high-resolution whole-genome sequencing and comparative genomics to identify key genetic features of the letters' Bacillus anthracis Ames strain. During systematic microbiological analysis of the spore material from the letters, we identified a number of morphological variants based on phenotypic characteristics and the ability to sporulate. The genomes of these morphological variants were sequenced and compared with that of the B. anthracis Ames ancestor, the progenitor of all B. anthracis Ames strains. Through comparative genomics, we identified four distinct loci with verifiable genetic mutations. Three of the four mutations could be directly linked to sporulation pathways in B. anthracis and more specifically to the regulation of the phosphorylation state of Spo0F, a key regulatory protein in the initiation of the sporulation cascade, thus linking phenotype to genotype. None of these variant genotypes were identified in single-colony environmental B. anthracis Ames isolates associated with the investigation. These genotypes were identified only in B. anthracis morphotypes isolated from the letters, indicating that the variants were not prevalent in the environment, not even the environments associated with the investigation. This study demonstrates the forensic value of systematic microbiological analysis combined with whole-genome sequencing and comparative genomics.

show abstract

The Program of Gene Transcription for a Single Differentiating Cell Type during Sporulation in Bacillus subtilis

Cited by 327 publications

References 106 publications

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

An essential transcription factor, SciP, enhances robustness of Caulobacter cell cycle regulation

Bacillus anthracis comparative genome analysis in support of the Amerithrax investigation

Contact Info

Product

Resources

About