Title:
Mammalian PIWIs and their involvement in germline epigenome modifications

 

Speaker:
Soichiro Yamanaka*, Hidetoshi Hasuwa, Kyoko Ishino and Haruhiko Siomi
Keio University School of Medicine
*present address: Dept. Biological Sciences, Graduate School of Science, The University of Tokyo

 

Abstract:
The PIWI-piRNA pathway is a conserved cellular pathway that represses transposable elements (TEs) and plays an important role in germline development. In mice, PIWI proteins are expressed almost exclusively in testes and not in ovaries. PIWI KO mice exhibit defects in spermatogenesis, leading to male infertility.

 

Topics 1: Two of mouse three PIWIs (Miwi2 and Mili) are highly expressed in gonocyte, which are embryonic male germ cells, and they are involved in DNA methylation. However, how the chromatin state of gonocyte is reorganized after the global reprogramming event and how the PIWIs function in the process are mostly unclear. We have discovered that transient opening of large TE-rich heterochromatin regions with mega-bases in size, termed DADs (differentially accessible domains), in gonocyte. Moreover, the global 3D chromosome organization is untangled, leading to relaxed chromatin state which accepts the genome wide de novo DNA methylation. The Piwi-piRNA pathway induces local chromatin compaction on a fraction of TEs within open DADs, forming a complex regulatory network for these genomic parasites in gonocyte. These data support a model in which, although it is counterintuitive, the Piwi–piRNA pathway initially represses de novo DNA methylation by inducing local chromatin compaction within DADs, which leads to delalyed DNA methylation on piRNA-target TEs in gonocyte.

 

Topics 2: In mice, PIWI proteins are expressed almost exclusively in testes and not in ovaries. However, recent studies have shown that many other mammals including humans express PIWIs both in testes and ovaries. To understand possible roles of PIWI proteins in mammalian ovaries, we have used the golden hamster (Syrian hamster; Mesocricetus auratus) in which three of its four distinct PIWIs (PIWIL1, 2, 3, and 4) are expressed in the ovary. We have recently generated PIWI KO hamsters using the CRISPR-Cas9 system. It was found that PIWIL1 KO female are infertile and PIWIL3 KO female are semi-fertile. Currently, we are engaged in examining defects in oogenesis (and other processes) in KO hamsters. I would like to present the results in the meeting.