hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans

Abstract Nematode development is characterized by progression through several larval stages. Thousands of genes were found in large scale RNAi-experiments to block this development at certain steps, two of which target the molecular chaperone HSP-90 and its cofactor UNC-45. Aiming to define the caus...

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Autores principales:	Lukas Schmauder, Klaus Richter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5744715a86b4487883c140e8a8348f55
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spelling	oai:doaj.org-article:5744715a86b4487883c140e8a8348f552021-12-02T17:39:49Zhsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans10.1038/s41598-021-91690-62045-2322https://doaj.org/article/5744715a86b4487883c140e8a8348f552021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91690-6https://doaj.org/toc/2045-2322Abstract Nematode development is characterized by progression through several larval stages. Thousands of genes were found in large scale RNAi-experiments to block this development at certain steps, two of which target the molecular chaperone HSP-90 and its cofactor UNC-45. Aiming to define the cause of arrest, we here investigate the status of nematodes after treatment with RNAi against hsp-90 and unc-45 by employing an in-depth transcriptional analysis of the arrested larvae. To identify misregulated transcriptional units, we calculate and validate genome-wide coexpression cliques covering the entire nematode genome. We define 307 coexpression cliques and more than half of these can be related to organismal functions by GO-term enrichment, phenotype enrichment or tissue enrichment analysis. Importantly, hsp-90 and unc-45 RNAi induce or repress many of these cliques in a coordinated manner, and then several specifically regulated cliques are observed. To map the developmental state of the arrested nematodes we define the expression behaviour of each of the cliques during development from embryo to adult nematode. hsp-90 RNAi can be seen to arrest development close to the L4 larval stage with further deviations in daf-16 regulated genes. unc-45 RNAi instead leads to arrested development at young adult stage prior to the programmatic downregulation of sperm-cell specific genes. In both cases processes can be defined to be misregulated upon depletion of the respective chaperone. With most of the defined gene cliques showing concerted behaviour at some stage of development from embryo to late adult, the “clique map” together with the clique-specific GO-terms, tissue and phenotype assignments will be a valuable tool in understanding concerted responses on the genome-wide level in Caenorhabditis elegans.Lukas SchmauderKlaus RichterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lukas Schmauder Klaus Richter hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans
description	Abstract Nematode development is characterized by progression through several larval stages. Thousands of genes were found in large scale RNAi-experiments to block this development at certain steps, two of which target the molecular chaperone HSP-90 and its cofactor UNC-45. Aiming to define the cause of arrest, we here investigate the status of nematodes after treatment with RNAi against hsp-90 and unc-45 by employing an in-depth transcriptional analysis of the arrested larvae. To identify misregulated transcriptional units, we calculate and validate genome-wide coexpression cliques covering the entire nematode genome. We define 307 coexpression cliques and more than half of these can be related to organismal functions by GO-term enrichment, phenotype enrichment or tissue enrichment analysis. Importantly, hsp-90 and unc-45 RNAi induce or repress many of these cliques in a coordinated manner, and then several specifically regulated cliques are observed. To map the developmental state of the arrested nematodes we define the expression behaviour of each of the cliques during development from embryo to adult nematode. hsp-90 RNAi can be seen to arrest development close to the L4 larval stage with further deviations in daf-16 regulated genes. unc-45 RNAi instead leads to arrested development at young adult stage prior to the programmatic downregulation of sperm-cell specific genes. In both cases processes can be defined to be misregulated upon depletion of the respective chaperone. With most of the defined gene cliques showing concerted behaviour at some stage of development from embryo to late adult, the “clique map” together with the clique-specific GO-terms, tissue and phenotype assignments will be a valuable tool in understanding concerted responses on the genome-wide level in Caenorhabditis elegans.
format	article
author	Lukas Schmauder Klaus Richter
author_facet	Lukas Schmauder Klaus Richter
author_sort	Lukas Schmauder
title	hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans
title_short	hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans
title_full	hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans
title_fullStr	hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans
title_full_unstemmed	hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans
title_sort	hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of c. elegans
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5744715a86b4487883c140e8a8348f55
work_keys_str_mv	AT lukasschmauder hsp90andunc45depletioninducecharacteristictranscriptionalsignaturesincoexpressioncliquesofcelegans AT klausrichter hsp90andunc45depletioninducecharacteristictranscriptionalsignaturesincoexpressioncliquesofcelegans
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hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans

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