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

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 imagin...

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Autores principales: Hoppe, Caroline, Bowles, Jonathan R., Minchington, Thomas G., Sutcliffe, Catherine, Upadhyai, Priyanka, Rattray, Magnus, Ashe, Hilary L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527239/
https://www.ncbi.nlm.nih.gov/pubmed/32758422
http://dx.doi.org/10.1016/j.devcel.2020.07.007
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author Hoppe, Caroline
Bowles, Jonathan R.
Minchington, Thomas G.
Sutcliffe, Catherine
Upadhyai, Priyanka
Rattray, Magnus
Ashe, Hilary L.
author_facet Hoppe, Caroline
Bowles, Jonathan R.
Minchington, Thomas G.
Sutcliffe, Catherine
Upadhyai, Priyanka
Rattray, Magnus
Ashe, Hilary L.
author_sort Hoppe, Caroline
collection PubMed
description 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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spelling pubmed-75272392020-10-05 Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo Hoppe, Caroline Bowles, Jonathan R. Minchington, Thomas G. Sutcliffe, Catherine Upadhyai, Priyanka Rattray, Magnus Ashe, Hilary L. Dev Cell Article 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. Cell Press 2020-09-28 /pmc/articles/PMC7527239/ /pubmed/32758422 http://dx.doi.org/10.1016/j.devcel.2020.07.007 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hoppe, Caroline
Bowles, Jonathan R.
Minchington, Thomas G.
Sutcliffe, Catherine
Upadhyai, Priyanka
Rattray, Magnus
Ashe, Hilary L.
Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
title Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
title_full Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
title_fullStr Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
title_full_unstemmed Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
title_short Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
title_sort modulation of the promoter activation rate dictates the transcriptional response to graded bmp signaling levels in the drosophila embryo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527239/
https://www.ncbi.nlm.nih.gov/pubmed/32758422
http://dx.doi.org/10.1016/j.devcel.2020.07.007
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