Zhuang Qinwei Kim-Wee, Bauermeister Klara, Galvez Jose Hector, Alogayil Najla, Batdorj Enkhjin, de Villena Fernando Pardo Manuel, Taketo Teruko, Bourque Guillaume, Naumova Anna K
Department of Human Genetics, McGill University, Montreal, QC, H3A 1C7, Canada.
Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto, 606-8303, Japan.
Genome Biol. 2025 Mar 26;26(1):74. doi: 10.1186/s13059-025-03547-0.
Sex-biased gene regulation is the basis of sexual dimorphism in phenotypes and has been studied across different cell types and different developmental stages. However, sex-biased expression of transposable elements (TEs), which represent nearly half of the mammalian genome and have the potential of influencing genome integrity and regulation, remains underexplored.
We report a survey of gene, lncRNA, and TE expression in four organs from mice with different combinations of gonadal and genetic sex. The data show remarkable variability among organs with respect to the impact of gonadal sex on transcription with the strongest effects observed in the liver. In contrast, the X-chromosome dosage alone had a modest influence on sex-biased transcription across organs, albeit interaction between X-dosage and gonadal sex cannot be ruled out. The presence of the Y-chromosome influences TE, but not gene or lncRNA, expression in the liver. Notably, 90% of sex-biased TEs (sDETEs) reside in clusters. Moreover, 54% of these clusters overlap or reside less than 100 kb from sex-biased genes or lncRNAs, share the same sex bias, and also have higher expression levels than sDETE clusters that do not co-localize with other types of sex-biased transcripts. We test the heterochromatic sink hypothesis that predicts higher expression of TEs in XX individuals finding no evidence to support it.
Our data show that sex-biased expression of TEs varies among organs with the highest numbers of sDETEs found in the liver following trends observed for genes and lncRNAs. It is enhanced by proximity to other types of sex-biased transcripts.
性别偏向性基因调控是表型性别二态性的基础，已在不同细胞类型和不同发育阶段进行了研究。然而，转座元件（TE）的性别偏向性表达仍未得到充分探索，转座元件占哺乳动物基因组的近一半，具有影响基因组完整性和调控的潜力。
我们报告了一项对具有不同性腺和遗传性别组合的小鼠四个器官中基因、长链非编码RNA（lncRNA）和TE表达的调查。数据显示，性腺性别对转录的影响在不同器官之间存在显著差异，在肝脏中观察到的影响最强。相比之下，仅X染色体剂量对各器官的性别偏向性转录影响较小，尽管不能排除X染色体剂量与性腺性别的相互作用。Y染色体的存在影响肝脏中TE的表达，但不影响基因或lncRNA的表达。值得注意的是，90%的性别偏向性TE（sDETE）位于簇中。此外，这些簇中有54%与性别偏向性基因或lncRNA重叠或位于其100 kb以内，具有相同的性别偏向性，并且其表达水平也高于不与其他类型性别偏向性转录本共定位的sDETE簇。我们测试了异染色质汇聚假说，该假说预测XX个体中TE的表达更高，但未找到支持该假说的证据。
我们的数据表明，TE的性别偏向性表达在不同器官之间存在差异，肝脏中发现的sDETE数量最多，遵循基因和lncRNA观察到的趋势。与其他类型的性别偏向性转录本接近会增强这种表达。
