Morc1 re-establishes heterochromatin on activated transposons and shapes the host transcriptome in gonocytes

Uneme, Y.; Maeda, R.; Nakayama, G.; Narita, H.; Takeda, N.; Hiramatsu, R.; Nishihara, H.; Nakato, R.; Kanai, Y.; Araki, K.; Siomi, M. C.; Yamanaka, S.

doi:10.1101/2023.06.26.546627

bioRxiv · 10.1101/2023.06.26.546627

Morc1 re-establishes heterochromatin on activated transposons and shapes the host transcriptome in gonocytes

Uneme, Y.·Maeda, R.·Nakayama, G.·Narita, H.·Takeda, N.·Hiramatsu, R.·Nishihara, H.·Nakato, R.·Kanai, Y.·Araki, K.·Siomi, M. C.·Yamanaka, S.

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Abstract

Following reprogramming of DNA methylation, numerous transposable elements (TEs) are transiently activated in male prenatal gonocytes. Persistent expression of such TEs to adulthood leads to arrest of germ cell development. However, how these TEs are re-silenced has been unexplored. Here, we found that DNA-binding protein Morc1 re-established H3K9me3-marked heterochromatin on activated TEs, which involved methyltransferase SetDB1. Although Morc1 also triggered DNA methylation, the types of Morc1-targeted TEs for each epigenetic modification were different, suggesting that these two mechanisms were largely independent of each other. Significant overlap between TEs targeted by Morc1 and those by Miwi2, a nuclear PIWI protein, indicated that piRNA-loaded Miwi2 conferred target specificity to Morc1. Activated TEs drove transcription of adjacent genes by acting as ectopic cis-regulatory elements. Such a disrupting effect of TEs on the transcriptome was compensated by Morc1. Thus, Morc1 ensures proper interactions of TEs with host genes through re-establishment of heterochromatin in gonocytes.

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Uneme, Y., Maeda, R., Nakayama, G., Narita, H., Takeda, N., Hiramatsu, R., Nishihara, H., Nakato, R., Kanai, Y., Araki, K., Siomi, M. C., Yamanaka, S.. 2023-06-29. Morc1 re-establishes heterochromatin on activated transposons and shapes the host transcriptome in gonocytes. https://doi.org/10.1101/2023.06.26.546627

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