Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity

Insulin/IGF-1-like signaling (IIS) plays a crucial, conserved role in development, growth, reproduction, stress tolerance, and longevity. In <i>Caenorhabditis elegans,</i> the enhanced longevity under reduced insulin signaling (rIIS) is primarily regulated by the transcription factors (T...

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Autores principales:	Neha Kaushik, Soumya Rastogi, Sonia Verma, Deepak Pandey, Ashutosh Halder, Arnab Mukhopadhyay, Neeraj Kumar
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	FOXO/DAF-16 NRF-2/SKN-1 HSF1/HSF-1 insulin-IGF-1 signaling <i>daf-2</i> <i>C. elegans</i> Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c3a9ea83753a4049a93684ce7b38e681
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spelling	oai:doaj.org-article:c3a9ea83753a4049a93684ce7b38e6812021-11-25T17:56:50ZTranscriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity10.3390/ijms2222124621422-00671661-6596https://doaj.org/article/c3a9ea83753a4049a93684ce7b38e6812021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12462https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Insulin/IGF-1-like signaling (IIS) plays a crucial, conserved role in development, growth, reproduction, stress tolerance, and longevity. In <i>Caenorhabditis elegans,</i> the enhanced longevity under reduced insulin signaling (rIIS) is primarily regulated by the transcription factors (TFs) DAF-16/FOXO, SKN-1/Nrf-1, and HSF1/HSF-1. The specific and coordinated regulation of gene expression by these TFs under rIIS has not been comprehensively elucidated. Here, using RNA-sequencing analysis, we report a systematic study of the complexity of TF-dependent target gene interactions during rIIS under analogous genetic and experimental conditions. We found that DAF-16 regulates only a fraction of the <i>C. elegans</i> transcriptome but controls a large set of genes under rIIS; SKN-1 and HSF-1 show the opposite trend. Both of the latter TFs function as activators and repressors to a similar extent, while DAF-16 is predominantly an activator. For expression of the genes commonly regulated by TFs under rIIS conditions, DAF-16 is the principal determining factor, dominating over the other two TFs, irrespective of whether they activate or repress these genes. The functional annotations and regulatory networks presented in this study provide novel insights into the complexity of the gene regulatory networks downstream of the IIS pathway that controls diverse phenotypes, including longevity.Neha KaushikSoumya RastogiSonia VermaDeepak PandeyAshutosh HalderArnab MukhopadhyayNeeraj KumarMDPI AGarticleFOXO/DAF-16NRF-2/SKN-1HSF1/HSF-1insulin-IGF-1 signaling<i>daf-2</i><i>C. elegans</i>Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12462, p 12462 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FOXO/DAF-16 NRF-2/SKN-1 HSF1/HSF-1 insulin-IGF-1 signaling <i>daf-2</i> <i>C. elegans</i> Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	FOXO/DAF-16 NRF-2/SKN-1 HSF1/HSF-1 insulin-IGF-1 signaling <i>daf-2</i> <i>C. elegans</i> Biology (General) QH301-705.5 Chemistry QD1-999 Neha Kaushik Soumya Rastogi Sonia Verma Deepak Pandey Ashutosh Halder Arnab Mukhopadhyay Neeraj Kumar Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity
description	Insulin/IGF-1-like signaling (IIS) plays a crucial, conserved role in development, growth, reproduction, stress tolerance, and longevity. In <i>Caenorhabditis elegans,</i> the enhanced longevity under reduced insulin signaling (rIIS) is primarily regulated by the transcription factors (TFs) DAF-16/FOXO, SKN-1/Nrf-1, and HSF1/HSF-1. The specific and coordinated regulation of gene expression by these TFs under rIIS has not been comprehensively elucidated. Here, using RNA-sequencing analysis, we report a systematic study of the complexity of TF-dependent target gene interactions during rIIS under analogous genetic and experimental conditions. We found that DAF-16 regulates only a fraction of the <i>C. elegans</i> transcriptome but controls a large set of genes under rIIS; SKN-1 and HSF-1 show the opposite trend. Both of the latter TFs function as activators and repressors to a similar extent, while DAF-16 is predominantly an activator. For expression of the genes commonly regulated by TFs under rIIS conditions, DAF-16 is the principal determining factor, dominating over the other two TFs, irrespective of whether they activate or repress these genes. The functional annotations and regulatory networks presented in this study provide novel insights into the complexity of the gene regulatory networks downstream of the IIS pathway that controls diverse phenotypes, including longevity.
format	article
author	Neha Kaushik Soumya Rastogi Sonia Verma Deepak Pandey Ashutosh Halder Arnab Mukhopadhyay Neeraj Kumar
author_facet	Neha Kaushik Soumya Rastogi Sonia Verma Deepak Pandey Ashutosh Halder Arnab Mukhopadhyay Neeraj Kumar
author_sort	Neha Kaushik
title	Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity
title_short	Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity
title_full	Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity
title_fullStr	Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity
title_full_unstemmed	Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity
title_sort	transcriptome analysis of insulin signaling-associated transcription factors in <i>c. elegans</i> reveal their genome-wide target genes specificity and complexity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c3a9ea83753a4049a93684ce7b38e681
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Transcriptome Analysis of Insulin Signaling-Associated Transcription Factors in <i>C. elegans</i> Reveal Their Genome-Wide Target Genes Specificity and Complexity

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