Table1_Transposable elements acquire time- and sex-specific transcriptional and epigenetic signatures along mouse fetal gonad development.docx

Gonadal sex determination in mice is a complex and dynamic process, which is crucial for the development of functional reproductive organs. The expression of genes involved in this process is regulated by a variety of genetic and epigenetic mechanisms. Recently, there has been increasing evidence that transposable elements (TEs), which are a class of mobile genetic elements, play a significant role in regulating gene expression during embryogenesis and organ development. In this study, we aimed to investigate the involvement of TEs in the regulation of gene expression during mouse embryonic gonadal development. Through bioinformatics analysis, we aimed to identify and characterize specific TEs that operate as regulatory elements for sex-specific genes, as well as their potential mechanisms of regulation. We identified TE loci expressed in a time- and sex-specific manner along fetal gonad development that correlate positively and negatively with nearby gene expression, suggesting that their expression is integrated to the gonadal regulatory network. Moreover, chromatin accessibility and histone post-transcriptional modification analyses in differentiating supporting cells revealed that TEs are acquiring a sex-specific signature for promoter-, enhancer-, and silencer-like elements, with some of them being proximal to critical sex-determining genes. Altogether, our study introduces TEs as the new potential players in the gene regulatory network that controls gonadal development in mammals.

小鼠性腺性别决定是一个复杂且动态的过程，对于功能性生殖器官的发育至关重要。参与该过程的基因表达受多种遗传与表观遗传机制调控。近期越来越多研究表明，转座因子（transposable elements, TEs）作为一类可移动遗传元件，在胚胎发生与器官发育过程中对基因表达发挥重要调控作用。本研究旨在探究转座因子在小鼠胚胎性腺发育过程中对基因表达的调控作用。通过生物信息学分析，本研究旨在鉴定并表征可作为性别特异性基因调控元件的特定转座因子，并解析其潜在调控机制。本研究鉴定出在胎儿性腺发育过程中呈时间特异性与性别特异性表达的转座因子位点，这些位点与邻近基因的表达呈正相关与负相关关系，表明其表达已整合至性腺调控网络中。此外，对分化中支持细胞的染色质开放性与组蛋白转录后修饰分析显示，转座因子已获得启动子样、增强子样以及沉默子样元件的性别特异性特征，其中部分转座因子紧邻关键性别决定基因。综上，本研究揭示转座因子作为潜在的新型调控因子，参与调控哺乳动物性腺发育的基因调控网络。