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bioRxiv · 10.64898/2026.05.14.724656

Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation

Yap, R. E.·Ebot-Ojong, F.·Ameri-Solanky, A. J.·Lewis, Z. A.
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Abstract

In animals, plants, and some fungi, Polycomb Repressive Complex 2 (PRC2) catalyzes trimethylation of histone H3 lysine 27 (H3K27me3) to establish transcriptionally repressed chromatin. Here, we identify the histone acetyltransferase RTT109 as a key regulator of PRC2-repressed domains in the model fungus Neurospora crassa. Although RTT109 interacts with the VPS75 homolog Nucleosome Assembly Factor 2 (NAF-2), we show that proper structure and function of PRC2-methylated chromatin require RTT109 catalytic activity but are independent of NAF-2 and H3K56 acetylation. We further demonstrate that H3K27me3 can be stably propagated over multiple rounds of mitosis in the absence of sequence-specific PRC2 targeting, and that RTT109 is essential for maintenance of the repressed state. These findings uncover a replication-linked mechanism for epigenetic memory and establish RTT109 as a key regulator of Polycomb-mediated chromatin inheritance.

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Yap, R. E., Ebot-Ojong, F., Ameri-Solanky, A. J., Lewis, Z. A.. 2026-05-17. Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation. https://doi.org/10.64898/2026.05.14.724656

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