Transposable elements acquire time- and sex-specific transcriptional and epigenetic signatures along mouse fetal gonad development

Isabelle Stévant; Nitzan Gonen; Francis Poulat

doi:10.3389/fcell.2023.1327410

Transposable elements acquire time- and sex-specific transcriptional and epigenetic signatures along mouse fetal gonad development

Front Cell Dev Biol. 2024 Jan 12:11:1327410. doi: 10.3389/fcell.2023.1327410. eCollection 2023.

Authors

Isabelle Stévant^{1

2}, Nitzan Gonen¹, Francis Poulat²

Affiliations

¹ The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Israel.
² Institute of Human Genetics, CNRS UMR9002 University of Montpellier, Montpellier, France.

Abstract

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.

Keywords: gene expression regulation; gonads; ovary; sex determination; testis; transposable elements.

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was co-funded by the Israel Science Foundation (ISF_710_2020) and the European Union (ERC, EnhanceSex, 101039928). IS and NG were funded by the ISF and ERC. FP was funded by Agence Nationale de la Recherche (ANR): ANR-21-CE14-0061-01 and ANR-23-CE14-0012-01.