3D genome remodeling and homologous pairing during meiotic prophase of mouse oogenesis and spermatogenesis

We comprehensively compared the chromatin structures and transcriptomes in successive substages of female and male mouse meiotic prophase by using sisHi-C and RNA-Seq methods. Interestingly, the transcriptional change happened earlier than chromatin structures reprograming that chromatin structures largely maintained the pre-meiotic condition in leptotene. Also, compartments and TADs gradually disappeared and then slowly recovered in both oocytes and spermatocytes. We characterized the events of homologous chromosomes pairing and found homologues adopted two sex-conserved pairing strategies prior to and after leptotene-to-zygotene transition, which firstly contacted more frequently in LINE enriched compartment B and then switched to SINE enriched compartment A. The sexual difference of transcriptome was most obvious in late meiotic prophase, which reflected in gamete morphology and function differences. We also complemented marker genes for each substage of oocytes and spermatocytes meiotic prophase, and predicted the sex-specific meiotic functional genes, whose mutation or deletion may cause sex different effects on fertility. In summary, this study revealed the sexual similarities and dimorphic of higher-order chromatin architecture, homologous pairing and transcriptome during meiotic prophase of both oogenesis and spermatogenesis. Overall design: By crossing female C57BL/6NJ (mVenus-P2A-HA-Sycp3 transgene mice) to male PWK-PhJ mice, we successfully purified oocytes and spermatocytes at time-points enriched of specific meiotic prophase substages, with the help of FACS of SYCP3 signal from F1 hybrid mice (B6xPWK). Then we performed sisHi-C, RNA-Seq and ATAC-Seq.