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Identification of cis-regulatory modules encoding temporal dynamics during development

BACKGROUND: Developmental transcriptional regulatory networks are circuits of transcription factors (TFs) and cis-acting DNA elements (Cis Regulatory Modules, CRMs) that dynamically control expression of downstream genes. Comprehensive knowledge of these networks is an essential step towards our und...

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Autores principales: Potier, Delphine, Seyres, Denis, Guichard, Céline, Iche-Torres, Magali, Aerts, Stein, Herrmann, Carl, Perrin, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097164/
https://www.ncbi.nlm.nih.gov/pubmed/24972496
http://dx.doi.org/10.1186/1471-2164-15-534
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author Potier, Delphine
Seyres, Denis
Guichard, Céline
Iche-Torres, Magali
Aerts, Stein
Herrmann, Carl
Perrin, Laurent
author_facet Potier, Delphine
Seyres, Denis
Guichard, Céline
Iche-Torres, Magali
Aerts, Stein
Herrmann, Carl
Perrin, Laurent
author_sort Potier, Delphine
collection PubMed
description BACKGROUND: Developmental transcriptional regulatory networks are circuits of transcription factors (TFs) and cis-acting DNA elements (Cis Regulatory Modules, CRMs) that dynamically control expression of downstream genes. Comprehensive knowledge of these networks is an essential step towards our understanding of developmental processes. However, this knowledge is mostly based on genome-wide mapping of transcription factor binding sites, and therefore requires prior knowledge regarding the TFs involved in the network. RESULTS: Focusing on how temporal control of gene expression is integrated within a developmental network, we applied an in silico approach to discover regulatory motifs and CRMs of co-expressed genes, with no prior knowledge about the involved TFs. Our aim was to identify regulatory motifs and potential trans-acting factors which regulate the temporal expression of co-expressed gene sets during a particular process of organogenesis, namely adult heart formation in Drosophila. Starting from whole genome tissue specific expression dynamics, we used an in silico method, cisTargetX, to predict TF binding motifs and CRMs. Potential Nuclear Receptor (NR) binding motifs were predicted to control the temporal expression profile of a gene set with increased expression levels during mid metamorphosis. The predicted CRMs and NR motifs were validated in vivo by reporter gene essays. In addition, we provide evidence that three NRs modulate CRM activity and behave as temporal regulators of target enhancers. CONCLUSIONS: Our approach was successful in identifying CRMs and potential TFs acting on the temporal regulation of target genes. In addition, our results suggest a modular architecture of the regulatory machinery, in which the temporal and spatial regulation can be uncoupled and encoded by distinct CRMs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-534) contains supplementary material, which is available to authorized users.
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spelling pubmed-40971642014-07-18 Identification of cis-regulatory modules encoding temporal dynamics during development Potier, Delphine Seyres, Denis Guichard, Céline Iche-Torres, Magali Aerts, Stein Herrmann, Carl Perrin, Laurent BMC Genomics Research Article BACKGROUND: Developmental transcriptional regulatory networks are circuits of transcription factors (TFs) and cis-acting DNA elements (Cis Regulatory Modules, CRMs) that dynamically control expression of downstream genes. Comprehensive knowledge of these networks is an essential step towards our understanding of developmental processes. However, this knowledge is mostly based on genome-wide mapping of transcription factor binding sites, and therefore requires prior knowledge regarding the TFs involved in the network. RESULTS: Focusing on how temporal control of gene expression is integrated within a developmental network, we applied an in silico approach to discover regulatory motifs and CRMs of co-expressed genes, with no prior knowledge about the involved TFs. Our aim was to identify regulatory motifs and potential trans-acting factors which regulate the temporal expression of co-expressed gene sets during a particular process of organogenesis, namely adult heart formation in Drosophila. Starting from whole genome tissue specific expression dynamics, we used an in silico method, cisTargetX, to predict TF binding motifs and CRMs. Potential Nuclear Receptor (NR) binding motifs were predicted to control the temporal expression profile of a gene set with increased expression levels during mid metamorphosis. The predicted CRMs and NR motifs were validated in vivo by reporter gene essays. In addition, we provide evidence that three NRs modulate CRM activity and behave as temporal regulators of target enhancers. CONCLUSIONS: Our approach was successful in identifying CRMs and potential TFs acting on the temporal regulation of target genes. In addition, our results suggest a modular architecture of the regulatory machinery, in which the temporal and spatial regulation can be uncoupled and encoded by distinct CRMs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-534) contains supplementary material, which is available to authorized users. BioMed Central 2014-06-27 /pmc/articles/PMC4097164/ /pubmed/24972496 http://dx.doi.org/10.1186/1471-2164-15-534 Text en © Potier et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Potier, Delphine
Seyres, Denis
Guichard, Céline
Iche-Torres, Magali
Aerts, Stein
Herrmann, Carl
Perrin, Laurent
Identification of cis-regulatory modules encoding temporal dynamics during development
title Identification of cis-regulatory modules encoding temporal dynamics during development
title_full Identification of cis-regulatory modules encoding temporal dynamics during development
title_fullStr Identification of cis-regulatory modules encoding temporal dynamics during development
title_full_unstemmed Identification of cis-regulatory modules encoding temporal dynamics during development
title_short Identification of cis-regulatory modules encoding temporal dynamics during development
title_sort identification of cis-regulatory modules encoding temporal dynamics during development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097164/
https://www.ncbi.nlm.nih.gov/pubmed/24972496
http://dx.doi.org/10.1186/1471-2164-15-534
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