open access

https://doi.org/10.14943/doctoral.r7213

https://hdl.handle.net/2115/93399

RNAi依存的ヘテロクロマチン形成における転写活性化因子としてのMoc3に関する研究

英語

2024-09-25

Hokkaido University

51p.

Transcription from pericentromeric heterochromatin and its transcripts have crucial roles in diverse cellular processes such as heterochromatin establishment, heterochromatin maintenance, genome stability, and early embryo development. In higher eukaryotes, the misregulation of transcription from heterochromatin results in cancers and other harmful diseases. In fission yeast Schizosaccharomyces pombe, heterochromatin is established and maintained primarily by RNA interference (RNAi) dependent system. A core process of RNAi-dependent heterochromatin formation is widely conserved in various eukaryotes; the production of small interfering RNA (siRNA) and the targeting of siRNA-bound Argonaute to chromatin using its sequence complementarity. In addition, transcription from heterochromatin by RNA polymerase II is critical for providing substrates for siRNA synthesis and a platform for assembling RNAi factors. However, the detailed mechanism of transcriptional regulation and the transcription factors are still unclear. To date, various heterochromatin factors have been identified by genetic screening using fission yeast. Here, we attempted to find novel genes whose products are involved in the transcriptional regulation of pericentromeric heterochromatin by reverse genetic screening. In the screening, we found that a zinc finger protein Moc3 localizes pericentromeric heterochromatin through its zinc finger domain. It activates strand-specific transcription when heterochromatin structure or heterochromatin-dependent silencing is compromised. Although Moc3 is not essential for heterochromatin maintenance, the absence of Moc3 significantly reduces the efficient establishment of heterochromatin. These results indicate that Moc3 acts as a transcriptional activator of pericentromeric heterochromatin to induce RNAi-dependent heterochromatin establishment.

2024-09-25

乙第7213号

博士(理学)

(主査) 特任教授 坂口 和靖, 教授 髙岡 晃教, 教授 松本 謙一郎, 教授 茂木 文夫

総合化学院

博士論文

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