1: Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing

EMBO JOURNAL,

38 (17):10.15252/embj.2019102870 SEP 2 2019

Murano, K; Iwasaki, YW; Ishizu, H; Mashiko, A; Shibuya, A; Kondo, S; Adachi, S; Suzuki, S; Saito, K; Natsume, T; Siomi, MC; Siomi, H

Dev Cell.

2019 Oct 7;51(1):21-34.e5. doi: 10.1016

Yamanaka S, Nishihara H, Toh H, Eijy Nagai LA, Hashimoto K, Park SJ, Shibuya A, Suzuki AM, Tanaka Y, Nakai K, Carninci P, Sasaki H, Siomi H

The Department of Molecular Biology has published two papers on the epigenetic regulation of transposons. The PIWI protein, expressed in germline tissues, and piRNA, a small non-coding RNA, are known as a mechanism for selectively repressing transposons. In the first paper (Paper 1), we found that Nxf2, an ovary-specific member of the nuclear RNA export factor family, contributes to the transcriptional silencing of transposons by piRNA, rather than performing nuclear export as its domain structure would suggest. Furthermore, we proposed a new two-step regulatory model in which Piwi-piRNA first represses the transcription of target transposons via Nxf2, and then this repressed state is maintained through mechanisms such as histone modification (Figure 1). In addition to the above findings, we also discovered that transposons, which are normally repressed, are transiently activated in male germ cells (gonocytes) during the fetal period in mice (Paper 2). Unlike in flies, the mouse genome undergoes DNA methylation. The methylome is established in gonocytes, but many aspects of this process remain unclear. We therefore analyzed gonocyte chromatin and discovered that the chromatin adopts a relaxed structure prior to DNA methylation. Ultimately, we proposed a model in which transposons act as the starting point for this structural change and methylome establishment (Figure 2).

(Haruhiko Siomi, Department of Molecular Biology, Class of 1986)