A kinetic mechanism for Drosophila bicoid cooperative binding

Lopes, Francisco J. P.; Vanario-Alonso, Carlos E.; Bisch, Paulo Mascarello; Vieira, Fernando M. C.

doi:10.1016/j.jtbi.2005.01.002

Cited by 14 publications

(7 citation statements)

References 31 publications

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“…It was shown that an ~300 bp region upstream of the hb coding region, the core part of the proximal promoter, that contains 6 main Bcd sites is sufficient to confer full regulation of hb by Bcd (Driever et al, 1989; Schroder et al, 1988; Struhl et al, 1989). Cooperative binding of Bcd to these six sites has also been previously demonstrated (Burz et al, 1998; Lopes et al, 2005; Ma et al, 1996). Moreover, to show that Bcd cooperative binding could determine the positioning of the hb pattern, Driever et al used a series of lacZ artificial constructs that were driven by fragments of the native hb promoter and contained different numbers of Bcd binding sites (Driever et al, 1989).…”

Section: Introductionmentioning

confidence: 56%

“…This morphogenetic protein determines positional information for downstream developmental genes such as hunchback ( hb ), Krüppel ( Kr ) and knirps ( kni ), which also show cross-regulation (Berleth et al, 1988; Crauk and Dostatni, 2005; de Lachapelle and Bergmann, 2010; Driever and Nusslein-Volhard, 1988; He et al, 2010a; Jäckle et al, 1986; Jaeger et al, 2004; Manu et al, 2009; Nusslein-Volhard et al, 1987; Papatsenko and Levine, 2011). It has been shown that cooperative binding is critical for Bcd transcriptional activity (Burz and Hanes, 2001; Burz et al, 1998; Driever et al, 1989; Lebrecht et al, 2005; Lopes et al, 2005; Lopes et al, 2008; Ma et al, 1996) and plays a central role in reducing transcriptional noise during Drosophila development (Holloway et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

“…This result was found even when an artificial construct was driven by 6 strong and 6 weak Bcd sites, which showed the strongest level of expression. Since these experiments, many efforts have been dedicated to characterizing the role of Bcd cooperative binding in hb pattern formation (Burz et al, 1998; Crauk and Dostatni, 2005; Gregor et al, 2007a; Lebrecht et al, 2005; Lopes et al, 2005; Lopes et al, 2008; Ma et al, 1996). …”

Section: Introductionmentioning

confidence: 99%

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The role of Bicoid cooperative binding in the patterning of sharp borders in Drosophila melanogaster

Lopes

Spirov

Bisch

2012

Developmental Biology

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In Drosophila embryonic development, the Bicoid (Bcd) protein establishes positional information of downstream developmental genes like hunchback (hb), which has a strong anterior expression and a sharp on-off boundary in the mid-embryo. The role of Bcd cooperative binding in the positioning of the Hb pattern has been previously demonstrated. However, there are discrepancies in the reported results about the role of this mechanism in the sharp Hb border. Here, we determined the Hill coefficient (nH) required for Bcd to generate the sharp border of Hb in wild-type (WT) embryos. We found that an nH of approximately 6.3 (s.d. 1.4) and 10.8 (s.d. 4.0) is required to account for Hb sharpness at early and late cycle 14A, respectively. Additional mechanisms are possibly required because the high nH is likely unachievable for Bcd binding to the hb promoter. To test this idea, we determined the nH required to pattern the Hb profile of 15 embryos expressing an hb14F allele that is defective in self-activation and found nH to be 3.0 (s.d. 1.0). This result indicates that in WT embryos, the hb self-activation is important for Hb sharpness. Corroborating our results, we also found a progressive increase in the required value of nH spanning from 4.0 to 9.2 by determining this coefficient from averaged profiles of eight temporal classes at cycle 14A (T1 to T8). Our results indicate that there is a transition in the mechanisms responsible for the sharp Hb border during cycle 14A: in early stages of this cycle, Bcd cooperative binding is primarily responsible for Hb sharpness; in late cycle 14A, hb self-activation becomes the dominant mechanism.

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Section: Introductionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of Bicoid cooperative binding in the patterning of sharp borders in Drosophila melanogaster

Lopes

Spirov

Bisch

2012

Developmental Biology

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“…(1)] gives a better¯t to early hb expression than does a simple,¯rst-order Bcd activation, in agreement with many published results on the cooperative nature of Bcd binding to form the early anterior hb pattern. 59,63,64 We tested the e®ect of adding Hb self-regulation to the basic Eq. (7) model À À À Hb self-activation has been shown to be involved in mid-NC14 sharpening of the Hb protein boundary at mid-embryo during NC14, both experimentally, with mutants, 64,65 and through modeling, 66 as well as diminishing expression noise.…”

Section: P2 In Early Nc14mentioning

confidence: 99%

Sequential construction of a model for modular gene expression control, applied to spatial patterning of theDrosophilagenehunchback

Spirov

Myasnikova

Holloway

2016

J. Bioinform. Comput. Biol.

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Gene network simulations are increasingly used to quantify mutual gene regulation in biological tissues. These are generally based on linear interactions between single-entity regulatory and target genes. Biological genes, by contrast, commonly have multiple, partially independent, cis-regulatory modules (CRMs) for regulator binding, and can produce variant transcription and translation products. We present a modeling framework to address some of the gene regulatory dynamics implied by this biological complexity. Spatial patterning of the hunchback (hb) gene in Drosophila development involves control by three CRMs producing two distinct mRNA transcripts. We use this example to develop a differential equations model for transcription which takes into account the cis-regulatory architecture of the gene. Potential regulatory interactions are screened by a genetic algorithms (GAs) approach and compared to biological expression data.

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“…The GRF of early anterior Hunchback expression with respect to Bcd ts a Hill function with coe cient 5-6. It has been widely assumed that this can be explained in terms of pairwise cooperative binding of Bcd to 6 sites in HbP2, with the Hill coe cient matching the number of sites (Burz et al, 1998;Driever et al, 1989;Gregor et al, 2007;Lopes et al, 2005;Ma et al, 1996) . We used our mathematical theory to prove that this assumption is unfounded.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity

Park

Estrada

Johnson

et al. 2018

Preprint

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Developmental enhancers integrate graded concentrations of input transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans factors that in uence the shape and position of expression driven by HbP2, and nd that the prevailing model, based on cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, mediator and histone modi ers in uence the shape and position of the HbP2 expression pattern. By comparing our results to theory, we assess how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be reexamined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function.

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A kinetic mechanism for Drosophila bicoid cooperative binding

Cited by 14 publications

References 31 publications

The role of Bicoid cooperative binding in the patterning of sharp borders in Drosophila melanogaster

The role of Bicoid cooperative binding in the patterning of sharp borders in Drosophila melanogaster

Sequential construction of a model for modular gene expression control, applied to spatial patterning of theDrosophilagenehunchback

Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity

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