Kinetic sculpting of the seven stripes of the Drosophila even-skipped gene

Berrocal, Augusto; Lammers, Nicholas C; García, Hernán G.; Eisen, Michael B.

doi:10.7554/elife.61635

Cited by 39 publications

(41 citation statements)

References 84 publications

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“…Transcriptionally silent loci that remain inactive throughout interphase, such as those revealed by our experiment (Fig. 3F), have been observed using MS2 (and its sister mRNA labeling tool, PP7) in live-imaging experiments in 2ies ( Garcia et al, 2013 ; Lammers et al, 2020 ; Berrocal et al, 2020 ), plants ( Alamos et al, 2020 ), and mammalian cells ( Hafner et al, 2020 ). However, it has not been possible to determine whether these inactive loci correspond to a separate transcriptional state from active loci, or whether they are an artifact of the 2uorescence detection thresholds associated with various microscopy techniques.…”

Section: Resultssupporting

confidence: 69%

Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient

Reimer

Álamos

Westrum

et al. 2021

Preprint

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How enhancers interpret morphogen gradients to generate spatial patterns of gene expression is a central question in developmental biology. Although recent studies have begun to elucidate that enhancers can dictate whether, when, and at what rate a promoter will engage in transcription, the complexity of endogenous enhancers calls for theoretical models with too many free parameters to quantitatively dissect these regulatory strategies. To overcome this limitation, we established a minimal synthetic enhancer system in embryos of the fruit 2y Drosophila melanogaster. Here, a gradient of the Dorsal activator is read by a single Dorsal binding site. By quantifying transcriptional activity using live imaging, our experiments revealed that this single Dorsal binding site is capable of regulating whether promoters engage in transcription in a Dorsal concentration-speci1c manner. By modulating binding-site aZnity, we determined that a gene’s decision to engage in transcription and its transcriptional onset time can be explained by a simple theoretical model where the promoter has to traverse multiple kinetic barriers before transcription can ensue. The experimental platform developed here pushes the boundaries of live-imaging in studying gene regulation in the early embryo by enabling the quanti1cation of the transcriptional activity driven by a single transcription factor binding site, and making it possible to build more complex enhancers from the ground up in the context of a dialogue between theory and experiment.

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Section: Resultssupporting

confidence: 69%

Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient

Reimer

Álamos

Westrum

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, nc14 was defined as the time between telophase of cleavage cycle 14 and the beginning of cephalic furrow formation. For the purpose of this study, nc14 was defined to last for 50 min similar to (Berrocal et al, 2018).…”

Section: Fish/smfish Microscopymentioning

confidence: 99%

Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo

et al. 2020

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Summary Morphogen gradients specify cell fates during development, with a classic example being the bone morphogenetic protein (BMP) gradient’s conserved role in embryonic dorsal-ventral axis patterning. Here, we elucidate how the BMP gradient is interpreted in the Drosophila embryo by combining live imaging with computational modeling to infer transcriptional burst parameters at single-cell resolution. By comparing burst kinetics in cells receiving different levels of BMP signaling, we show that BMP signaling controls burst frequency by regulating the promoter activation rate. We provide evidence that the promoter activation rate is influenced by both enhancer and promoter sequences, whereas Pol II loading rate is primarily modulated by the enhancer. Consistent with BMP-dependent regulation of burst frequency, the numbers of BMP target gene transcripts per cell are graded across their expression domains. We suggest that graded mRNA output is a general feature of morphogen gradient interpretation and discuss how this can impact on cell-fate decisions.

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“…In Drosophila, the burst duration is about 10-20 minutes (14,96,114,115). The sm-FISH has shown that in Drosophila gap genes, the mRNA is transcribed with the average residence time 3 min  and the gene is not expressed with a relatively longer lifetime.…”

Section: Gene States Switching Ratesmentioning

confidence: 99%

Theoretical Principles of Enhancer-Promoter Communication in Transcriptional Bursting

Wang

Zhang

Luo

et al. 2022

Preprint

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Transcriptional regulation occurs through genomic contacts between enhancers and their cognate promoters, and most genes are transcribed in a bursty fashion. To understand the relationship between these two phenomena, we develop a general modeling framework in terms of the information transmission from upstream genomic organization to downstream transcriptional bursting. Importantly, we uncover fundamental theoretical principles of enhancer-promoter (E-P) spatial communication in the modulation of transcriptional burst size (BS) and burst frequency (BF). First, BS and BF obey their respective power-law dependences on the E-P communication strength and distinct scaling exponents. Second, the E-P spatial distance follows a Maxwell-Boltzmann distribution rather than the previously assumed Gauss distribution. Third, the E-P genomic distance affects transcriptional outcomes biphasically (i.e., in an exponential decay for small E-P genomic distances but insensitively to large E-P genomic distances). Fourth, the E-P communication mainly modulates BF rather than BS. Finally, the mutual information between BS (or BF) and E-P spatial distance further reveals essential characteristics of the information transfer from the upstream to the downstream. Our predictions are experimentally verifiable, e.g., confirmed by experimental data on Drosophila. The overall analysis provides insights into the role of the E-P communication in the control of transcriptional bursting.

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Kinetic sculpting of the seven stripes of the Drosophila even-skipped gene

Cited by 39 publications

References 84 publications

Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient

Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient

Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo

Theoretical Principles of Enhancer-Promoter Communication in Transcriptional Bursting

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