Impact of LINEs, SINEs, and long non-coding RNAs on meiotic chromosome organization in female prophase I

• Applicant: Dr. Mathilde Biot, Ph.D.
• Subject Area: Cell Biology ; General Genetics and Functional Genome Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569072597

Meiosis is a specialized cell cycle essential for gamete production and genetic diversity. A diploid germ cell undergoes DNA replication followed by two divisions. In meiosis I, homologous chromosomes segregate, and in meiosis II, sister chromatids separate, producing haploid cells. The specificity of meiosis I arises from homolog pairing and recombination, initiated by programmed DNA double-strand breaks (DSBs). Concomitant with DSB formation, chromosomes in prophase I organize into loop arrays anchored to a proteinaceous axis, which serves as a platform for DSB activity. A key question is how this axis forms and which DNA sequences are involved. This has been mainly studied in males. During my PhD, I mapped axis-associated DNA in spermatocytes and identified three types: DSB sites, CTCF sites, and functional elements, mainly promoters. I also found a positive correlation between H3K4me3 enrichment and axis-associated sequences, highlighting the role of epigenetic marks in chromosome organization. In females, meiotic prophase I occurs in a distinct epigenetic context, with significantly lower DNA methylation than in males. Given the impact of epigenetic modifications on chromatin organization, this suggests sexual dimorphism in meiotic chromosome structure. However, how these differences affect chromosome organization in females remains unclear. My preliminary data reveal two unexpected observations: first, an enrichment of H3K4me3 at active LINE1 elements in female prophase I, absent in males; second, that oocytes remain transcriptionally active throughout prophase I, contradicting previous studies suggesting silencing. These findings raise the possibility that non-coding RNAs influence chromosome organization in female meiosis. The role of LINEs and SINEs in meiosis has long been debated due to their potential to transpose and impact genome stability. While they contribute to 3D genome organization in somatic cells, their role in meiosis remains unclear. Interestingly, a study in S. pombe suggests that long non-coding RNAs influence chromosome organization by recruiting RNA-binding proteins to facilitate homolog pairing. My preliminary data could align with this, proposing that active LINE elements are transcribed in female prophase I and associated with H3K4me3 enrichment, potentially contributing to axis formation. In this proposal, I would like to investigate the role of LINEs, SINEs, and long non-coding RNAs in female meiotic chromosome organization. By examining their impact on homolog pairing, synapsis, and genome organization, this research will provide new insights into female meiosis and sexual dimorphism in chromatin structure. Additionally, it will contribute to understanding repetitive element regulation, genome stability, and meiotic recombination, informing future studies in reproductive biology and genome evolution.

• DFG Programme: WBP Position