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Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila
The ecdysone pathway was among the first experimental systems employed to study the impact of steroid hormones on the genome. In Drosophila and other insects, ecdysone coordinates developmental transitions, including wholesale transformation of the larva into the adult during metamorphosis. Like oth...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525475/ https://www.ncbi.nlm.nih.gov/pubmed/31019084 http://dx.doi.org/10.1073/pnas.1900343116 |
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author | Uyehara, Christopher M. McKay, Daniel J. |
author_facet | Uyehara, Christopher M. McKay, Daniel J. |
author_sort | Uyehara, Christopher M. |
collection | PubMed |
description | The ecdysone pathway was among the first experimental systems employed to study the impact of steroid hormones on the genome. In Drosophila and other insects, ecdysone coordinates developmental transitions, including wholesale transformation of the larva into the adult during metamorphosis. Like other hormones, ecdysone controls gene expression through a nuclear receptor, which functions as a ligand-dependent transcription factor. Although it is clear that ecdysone elicits distinct transcriptional responses within its different target tissues, the role of its receptor, EcR, in regulating target gene expression is incompletely understood. In particular, EcR initiates a cascade of transcription factor expression in response to ecdysone, making it unclear which ecdysone-responsive genes are direct EcR targets. Here, we use the larval-to-prepupal transition of developing wings to examine the role of EcR in gene regulation. Genome-wide DNA binding profiles reveal that EcR exhibits widespread binding across the genome, including at many canonical ecdysone response genes. However, the majority of its binding sites reside at genes with wing-specific functions. We also find that EcR binding is temporally dynamic, with thousands of binding sites changing over time. RNA-seq reveals that EcR acts as both a temporal gate to block precocious entry to the next developmental stage as well as a temporal trigger to promote the subsequent program. Finally, transgenic reporter analysis indicates that EcR regulates not only temporal changes in target enhancer activity but also spatial patterns. Together, these studies define EcR as a multipurpose, direct regulator of gene expression, greatly expanding its role in coordinating developmental transitions. |
format | Online Article Text |
id | pubmed-6525475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-65254752019-05-28 Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila Uyehara, Christopher M. McKay, Daniel J. Proc Natl Acad Sci U S A PNAS Plus The ecdysone pathway was among the first experimental systems employed to study the impact of steroid hormones on the genome. In Drosophila and other insects, ecdysone coordinates developmental transitions, including wholesale transformation of the larva into the adult during metamorphosis. Like other hormones, ecdysone controls gene expression through a nuclear receptor, which functions as a ligand-dependent transcription factor. Although it is clear that ecdysone elicits distinct transcriptional responses within its different target tissues, the role of its receptor, EcR, in regulating target gene expression is incompletely understood. In particular, EcR initiates a cascade of transcription factor expression in response to ecdysone, making it unclear which ecdysone-responsive genes are direct EcR targets. Here, we use the larval-to-prepupal transition of developing wings to examine the role of EcR in gene regulation. Genome-wide DNA binding profiles reveal that EcR exhibits widespread binding across the genome, including at many canonical ecdysone response genes. However, the majority of its binding sites reside at genes with wing-specific functions. We also find that EcR binding is temporally dynamic, with thousands of binding sites changing over time. RNA-seq reveals that EcR acts as both a temporal gate to block precocious entry to the next developmental stage as well as a temporal trigger to promote the subsequent program. Finally, transgenic reporter analysis indicates that EcR regulates not only temporal changes in target enhancer activity but also spatial patterns. Together, these studies define EcR as a multipurpose, direct regulator of gene expression, greatly expanding its role in coordinating developmental transitions. National Academy of Sciences 2019-05-14 2019-04-24 /pmc/articles/PMC6525475/ /pubmed/31019084 http://dx.doi.org/10.1073/pnas.1900343116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | PNAS Plus Uyehara, Christopher M. McKay, Daniel J. Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila |
title | Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila |
title_full | Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila |
title_fullStr | Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila |
title_full_unstemmed | Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila |
title_short | Direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila |
title_sort | direct and widespread role for the nuclear receptor ecr in mediating the response to ecdysone in drosophila |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525475/ https://www.ncbi.nlm.nih.gov/pubmed/31019084 http://dx.doi.org/10.1073/pnas.1900343116 |
work_keys_str_mv | AT uyeharachristopherm directandwidespreadroleforthenuclearreceptorecrinmediatingtheresponsetoecdysoneindrosophila AT mckaydanielj directandwidespreadroleforthenuclearreceptorecrinmediatingtheresponsetoecdysoneindrosophila |