Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, Finland.
Nucleic Acids Res. 2020 Jul 27;48(13):7135-7153. doi: 10.1093/nar/gkaa460.
Constitutive heterochromatin at the pericentric regions of chromosomes undergoes dynamic changes in its epigenetic and spatial organization during spermatogenesis. Accurate control of pericentric heterochromatin is required for meiotic cell divisions and production of fertile and epigenetically intact spermatozoa. In this study, we demonstrate that pericentric heterochromatin is expressed during mouse spermatogenesis to produce major satellite repeat (MSR) transcripts. We show that the endonuclease DICER localizes to the pericentric heterochromatin in the testis. Furthermore, DICER forms complexes with MSR transcripts, and their processing into small RNAs is compromised in Dicer1 knockout mice leading to an elevated level of MSR transcripts in meiotic cells. We also show that defective MSR forward transcript processing in Dicer1 cKO germ cells is accompanied with reduced recruitment of SUV39H2 and H3K9me3 to the pericentric heterochromatin and meiotic chromosome missegregation. Altogether, our results indicate that the physiological role of DICER in maintenance of male fertility extends to the regulation of pericentric heterochromatin through direct targeting of MSR transcripts.
着丝粒周围异染色质在精子发生过程中经历其表观遗传和空间组织的动态变化。准确控制着丝粒异染色质对于减数分裂细胞分裂和产生有活力和表观遗传完整的精子至关重要。在这项研究中，我们证明了着丝粒异染色质在小鼠精子发生过程中表达，产生主要卫星重复 (MSR) 转录本。我们表明内切核酸酶 DICER 在睾丸中定位于着丝粒异染色质。此外，DICER 与 MSR 转录本形成复合物，其加工成小 RNA 在 Dicer1 敲除小鼠中受到损害，导致减数分裂细胞中 MSR 转录本水平升高。我们还表明，Dicer1 cKO 生殖细胞中 MSR 前体转录本处理的缺陷伴随着 SUV39H2 和 H3K9me3 向着丝粒异染色质的募集减少和减数分裂染色体错误分离。总之，我们的结果表明 DICER 在维持男性生育力方面的生理作用通过直接靶向 MSR 转录本扩展到对着丝粒异染色质的调节。
