Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation
- 1Department of Microbiology, University of Georgia, Athens, Georgia, United States of America.
- 2Department of Genetics, University of Georgia, Athens, Georgia, United States of America.
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. Author summary: Proper development of multicellular organisms depends on the establishment and long-term maintenance of cell-type-specific gene expression programs. In eukaryotes, DNA is packaged with histone proteins to form chromatin, which can adopt different states that influence gene expression. In plants, animals, and some fungi, Polycomb Repressive Complexes (PRCs) assemble repressive chromatin that is important for stable gene silencing. How these chromatin states are inherited across cell divisions remains incompletely understood. We found that the fungal acetyltransferase RTT109, best known for modifying histones during DNA replication, is unexpectedly required for stability of PRC-repressed chromatin in the model fungus Neurospora crassa. Using a synthetic system that allows reversible recruitment of PRC2 to DNA, we show that the repressive histone modification H3K27me3 can persist through multiple mitotic divisions and that this persistence is disrupted in the absence of RTT109. Loss of RTT109 also disrupts a repressive histone modification deposited by the methyltransferase ASH1. Surprisingly, normal repressive chromatin patterns require RTT109 acetyltransferase activity but are independent of its major product, H3K56ac. Together, these findings reveal a new connection between a DNA replication-associated protein and epigenetic memory and provide insight into how stable Polycomb repression is maintained in fungi that lack the PRC1 complexes found in plants and animals.
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BibTeX
@article{yap2026epigenetic,
title = {{Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation}},
author = {Rochelle E Yap and Felicia Ebot-Ojong and Abigail J Ameri-Solanky and Zachary A Lewis},
journal = {PLOS Genetics},
year = {2026},
month = oct,
doi = {10.1371/journal.pgen.1012327},
url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012327},
note = {CC BY},
}
RIS
TY - JOUR
TI - Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation
AU - Rochelle E Yap
AU - Felicia Ebot-Ojong
AU - Abigail J Ameri-Solanky
AU - Zachary A Lewis
PY - 2026
DA - 2026/10/05
JO - PLOS Genetics
DO - 10.1371/journal.pgen.1012327
UR - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012327
AB - 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. Author summary: Proper development of multicellular organisms depends on the establishment and long-term maintenance of cell-type-specific gene expression programs. In eukaryotes, DNA is packaged with histone proteins to form chromatin, which can adopt different states that influence gene expression. In plants, animals, and some fungi, Polycomb Repressive Complexes (PRCs) assemble repressive chromatin that is important for stable gene silencing. How these chromatin states are inherited across cell divisions remains incompletely understood. We found that the fungal acetyltransferase RTT109, best known for modifying histones during DNA replication, is unexpectedly required for stability of PRC-repressed chromatin in the model fungus Neurospora crassa. Using a synthetic system that allows reversible recruitment of PRC2 to DNA, we show that the repressive histone modification H3K27me3 can persist through multiple mitotic divisions and that this persistence is disrupted in the absence of RTT109. Loss of RTT109 also disrupts a repressive histone modification deposited by the methyltransferase ASH1. Surprisingly, normal repressive chromatin patterns require RTT109 acetyltransferase activity but are independent of its major product, H3K56ac. Together, these findings reveal a new connection between a DNA replication-associated protein and epigenetic memory and provide insight into how stable Polycomb repression is maintained in fungi that lack the PRC1 complexes found in plants and animals.
SN - 1553-7404
SN - 1553-7390
ER -