Falker-Gieske Clemens, Mott Andrea, Franzenburg Sören, Tetens Jens
Department of Animal Sciences, Georg-August-University, Burckhardtweg 2, 37077, Göttingen, Germany.
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
BMC Genomics. 2021 Mar 2;22(1):146. doi: 10.1186/s12864-021-07451-2.
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.
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.
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.
视黄醇（RO）及其活性代谢产物视黄酸（RA）是脊椎动物基因表达的主要调节因子，影响器官发育、细胞分化和免疫反应等各种过程。为了表征脊椎动物中对RA暴露的一般转录组反应，不受物种和组织特异性影响，我们分析了来自智人、小家鼠和非洲爪蟾的四个公开可用的RNA测序数据集。为了增加物种和细胞类型的多样性，我们用鸡肝癌（LMH）细胞生成了RNA测序数据。此外，我们比较了LMH细胞在不同时间点对RA和RO的反应。
通过进行转录组元分析，我们鉴定出三个视黄酸反应核心簇（RARCC），由27种相互作用的蛋白质组成，其中七种尚未与类视黄醇相关联。比较LMH细胞在不同时间点对RO和RA暴露的转录反应，导致鉴定出仅在早期反应期间差异表达（DE）的非编码RNA（ncRNA）。
我们提出这些RARCCs处于脊椎动物中常见的RA调节层次结构的顶端。基于这些簇中包含的蛋白质集，我们能够鉴定出一个RA反应簇、一个控制中心类型簇和一个指导细胞增殖的簇。关于细胞对RA和RO反应的比较，我们得出结论，ncRNA在类视黄醇介导的基因调控中发挥着被低估的作用。
