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Multi-species transcriptome meta-analysis of the response to retinoic acid in vertebrates and comparative analysis of the effects of retinol and retinoic acid on gene expression in LMH cells

dc.contributor.authorFalker-Gieske, Clemens
dc.contributor.authorMott, Andrea
dc.contributor.authorFranzenburg, Sören
dc.contributor.authorTetens, Jens
dc.date.accessioned2021-03-07T04:23:23Z
dc.date.available2021-03-07T04:23:23Z
dc.date.issued2021
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/17740
dc.description.abstractBackground Retinol (RO) and its active metabolite retinoic acid (RA) are major regulators of gene expression in vertebrates and influence various processes like organ development, cell differentiation, and immune response. To characterize a general transcriptomic response to RA-exposure in vertebrates, independent of species- and tissue-specific effects, four publicly available RNA-Seq datasets from Homo sapiens, Mus musculus, and Xenopus laevis were analyzed. To increase species and cell-type diversity we generated RNA-seq data with chicken hepatocellular carcinoma (LMH) cells. Additionally, we compared the response of LMH cells to RA and RO at different time points. Results By conducting a transcriptome meta-analysis, we identified three retinoic acid response core clusters (RARCCs) consisting of 27 interacting proteins, seven of which have not been associated with retinoids yet. Comparison of the transcriptional response of LMH cells to RO and RA exposure at different time points led to the identification of non-coding RNAs (ncRNAs) that are only differentially expressed (DE) during the early response. Conclusions We propose that these RARCCs stand on top of a common regulatory RA hierarchy among vertebrates. Based on the protein sets included in these clusters we were able to identify an RA-response cluster, a control center type cluster, and a cluster that directs cell proliferation. Concerning the comparison of the cellular response to RA and RO we conclude that ncRNAs play an underestimated role in retinoid-mediated gene regulation.
dc.language.isoen
dc.publisherBioMed Central
dc.identifier.bibliographicCitationBMC Genomics. 2021 Mar 02;22(1):146
dc.rightsopenAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleMulti-species transcriptome meta-analysis of the response to retinoic acid in vertebrates and comparative analysis of the effects of retinol and retinoic acid on gene expression in LMH cells
dc.typejournalArticle
dc.identifier.doi10.1186/s12864-021-07451-2
dc.type.versionpublishedVersion
dc.date.updated2021-03-07T04:23:23Z
dc.rights.holderThe Author(s)
dc.bibliographicCitation.volume22
dc.bibliographicCitation.issue1
dc.type.subtypejournalArticle
dc.identifier.pmid33653267
dc.bibliographicCitation.articlenumber146
dc.bibliographicCitation.journalBMC Genomics


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