转录组和甲基组分析揭示了甲状腺激素和糖皮质激素信号在非洲爪蟾变态过程中的复杂相互作用。
Transcriptome and Methylome Analysis Reveal Complex Cross-Talks between Thyroid Hormone and Glucocorticoid Signaling at Xenopus Metamorphosis.
机构信息
UMR7221 Molecular Physiology and Adaption, CNRS, Museum National d'Histoire Naturelle, 57 Rue Cuvier, CEDEX 05, 75231 Paris, France.
Genomics Core Facility, Département de Biologie, Institut de Biologie de l'ENS (IBENS), École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France.
出版信息
Cells. 2021 Sep 9;10(9):2375. doi: 10.3390/cells10092375.
BACKGROUND
Most work in endocrinology focus on the action of a single hormone, and very little on the cross-talks between two hormones. Here we characterize the nature of interactions between thyroid hormone and glucocorticoid signaling during metamorphosis.
METHODS
We used functional genomics to derive genome wide profiles of methylated DNA and measured changes of gene expression after hormonal treatments of a highly responsive tissue, tailfin. Clustering classified the data into four types of biological responses, and biological networks were modeled by system biology.
RESULTS
We found that gene expression is mostly regulated by either T or CORT, or their additive effect when they both regulate the same genes. A small but non-negligible fraction of genes (12%) displayed non-trivial regulations indicative of complex interactions between the signaling pathways. Strikingly, DNA methylation changes display the opposite and are dominated by cross-talks.
CONCLUSION
Cross-talks between thyroid hormones and glucocorticoids are more complex than initially envisioned and are not limited to the simple addition of their individual effects, a statement that can be summarized with the pseudo-equation: TH GC > TH + GC. DNA methylation changes are highly dynamic and buffered from genome expression.
背景
大多数内分泌学的工作都集中在单一激素的作用上，而很少关注两种激素之间的相互作用。在这里，我们描述了甲状腺激素和糖皮质激素信号在变态过程中的相互作用的性质。
方法
我们使用功能基因组学来推导出甲基化 DNA 的全基因组图谱，并在高度敏感的组织尾鳍中测量激素处理后的基因表达变化。聚类将数据分为四种类型的生物学反应，并通过系统生物学来构建生物学网络。
结果
我们发现，基因表达主要是由 T 或 CORT 或它们同时调节相同基因时的加性效应来调节的。一小部分（12%）基因显示出复杂信号通路之间相互作用的非平凡调节，虽然比例较小，但不容忽视。令人惊讶的是，DNA 甲基化变化显示出相反的情况，主要是由信号通路之间的相互作用所主导。
结论
甲状腺激素和糖皮质激素之间的相互作用比最初设想的要复杂得多，不仅仅局限于它们各自作用的简单相加，这一说法可以用伪方程概括：TH GC > TH + GC。DNA 甲基化变化是高度动态的，并与基因组表达相隔离。
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