Gene and transposon transcription patterns in mouse organs highlight shared and organ-specific sex-biased regulation

Males and females differ in many aspects of their biology. To understand how sexual dimorphism in phenotypes arises, sex-biased gene regulation has been studied in both mice and humans across different cell types and different developmental stages. However, sex-biased expression of transposable elements (TEs) that represent nearly half of the mammalian genome and have the potential of influencing genome integrity and regulation, remains underexplored. Here, we report a survey of sex-biased expression of both genes and transposable elements (TEs) in four organs (brain, heart, lung, and liver) in mice with different combinations of gonadal sex and sex-chromosome complement that allow separating the influences of gonadal sex and sex chromosomes. We find remarkable variability among organs with respect to the impact of gonadal sex on transcription of both genes and TEs with the strongest effects observed in liver. In contrast, the X-chromosome dosage alone had modest influence on sex-biased transcription across different organs, albeit interaction between X-dosage and gonadal sex cannot be ruled out. The presence of the Y chromosome influenced TE, but not gene expression in liver. We also find that 90% of sex-biased TEs reside in clusters, whereas about 50% co-localize with sex-biased genes and share the same bias direction. These data imply that regulation of sex-biased TEs is often associated and concordant with that of sex-biased genes. Whether such a relationship also exists for non-sex-biased expression remains to be determined and may be of interest for understanding the pathogenesis of diseases associated with TEs in humans. Finally, we tested the heterochromatic sink hypothesis that predicts higher expression of genes and TEs in XX individuals and found no evidence to support it. Mice with different combinations of sex-chromosome complement and gonadal sex were generated using crosses between B6.YTIR males and C57BL/6J females (B6.YTIR cross) as well as B6.C3H/HeSn-Paf males with C57BL/6J females (XPaf cross). Liver, lung parenchyma, heart, and whole brain were collected from 8-week old mice and used for RNA extraction. Gonadal sex was confirmed at the time of organ collection.