{ "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.", "abstract_shown": true, "affiliations": [ "Department of Microbiology, University of Georgia, Athens, Georgia, United States of America.", "Department of Genetics, University of Georgia, Athens, Georgia, United States of America." ], "article_type": "Research Article", "arxiv": null, "author_total": 4, "authors": [ { "affs": [ 0 ], "name": "Rochelle E Yap", "orcid": "0000-0002-9181-280X" }, { "affs": [ 1 ], "name": "Felicia Ebot-Ojong", "orcid": "0000-0002-3408-3487" }, { "affs": [ 0 ], "name": "Abigail J Ameri-Solanky" }, { "affs": [ 0, 1 ], "name": "Zachary A Lewis", "orcid": "0000-0002-1735-8266" } ], "bibtex": "https://research.draconitic.com/paper/ar6knmb6qavxk.bib", "cited_by": 0, "doi": "10.1371/journal.pgen.1012327", "fulltext_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012327", "id": "ar6knmb6qavxk", "issns": [ "1553-7404", "1553-7390" ], "landing_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012327", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "1312|Epigenetics and DNA Methylation" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Histones" ], [ "plos", "/Biology and life sciences/Cell biology/Chromosome biology/Chromatin" ], [ "plos", "/Biology and life sciences/Cell biology/Chromosome biology/Chromatin/Heterochromatin" ], [ "plos", "/Biology and life sciences/Genetics/Epigenetics/Chromatin" ], [ "plos", "/Biology and life sciences/Genetics/Epigenetics/Chromatin/Heterochromatin" ], [ "plos", "/Biology and life sciences/Genetics/Fungal genetics" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Chromatin" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Chromatin/Heterochromatin" ], [ "plos", "/Biology and life sciences/Genetics/Genomics" ], [ "plos", "/Biology and life sciences/Microbiology/Microbial control/Antimicrobials/Antibiotics/Tetracyclines" ], [ "plos", "/Biology and life sciences/Mycology/Fungal genetics" ], [ "plos", "/Biology and life sciences/Organisms/Eukaryota/Fungi" ], [ "plos", "/Biology and life sciences/Organisms/Eukaryota/Fungi/Neurospora/Neurospora crassa" ], [ "plos", "/Medicine and health sciences/Pharmacology/Drugs/Antimicrobials/Antibiotics/Tetracyclines" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Neurospora crassa" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Yeast and fungal models/Neurospora crassa" ], [ "plos", "/Research and analysis methods/Model organisms/Neurospora crassa" ] ], "openalex": "W7220452086", "pdf_url": "https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1012327&type=printable", "pmcid": "PMC13652317", "pmid": "42832562", "published": "2026-10-05", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/ar6knmb6qavxk.ris", "sources": [ { "first_seen": "2026-10-30T12:17:37Z", "native_id": "10.1371/journal.pgen.1012327", "source": "plos", "url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012327" }, { "first_seen": "2026-10-30T12:18:10Z", "native_id": "MED:42832562", "source": "europepmc", "url": "https://europepmc.org/article/MED/42832562" } ], "subjects": [ { "field": "biochemistry", "origin": "plos:gene expression", "subfield": "molecular-biology" }, { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:genetics", "subfield": "genetics-genomics" } ], "title": "Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation", "title_text": "Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:10Z", "url": "https://research.draconitic.com/paper/ar6knmb6qavxk", "venue": "PLOS Genetics", "versions": [] }