PLoS Genetics最新文献

{"title":"An NKX2-3/5/6 homolog is required downstream of BMP signaling to pattern the sensory-adhesive organ of a tunicate larva.","authors":"Christopher J Johnson, Joshua Kavaler, Timethea Slade, Kayla Wilson, Christina D Cota, Alberto Stolfi","doi":"10.1371/journal.pgen.1012334","DOIUrl":"10.1371/journal.pgen.1012334","url":null,"abstract":"<p><p>Tunicates are the sister group to vertebrates within the chordate phylum, yet unlike other chordate groups, they evolved a biphasic lifecycle alternating between motile larvae and sessile adults. The papillae of most tunicate larvae are the key sensory-adhesive organ regulating their settlement and metamorphosis. The papillae are nearly always arranged as a group of three morphologically identical organs that arise from an anterior neural plate border region nested between ventral epidermis and more dorsal/posterior neural tube progenitors. Due to their embryonic origin and molecular signatures, this anterior border has been evolutionarily linked to vertebrate placode regions. It was previously shown that the specification, patterning, and morphogenesis of the embryonic papilla region all depend on BMP signaling, though downstream mechanisms remain poorly understood. Here we show that the NKX2-3/5/6 ortholog NK4 is a key transcription factor that acts downstream of BMP signaling to pattern the papillae in the Ciona embryo. We present evidence that NK4 is activated by BMP signaling and encodes a transcriptional repressor that is required to restrict the expression of the papilla regulatory gene Foxg to three cell clusters that give rise to the three papillae. Loss of NK4 function results in the formation of a single large papilla. In contrast, overexpression of NK4 represses Foxg, eliminating the papillae. We also show that the expression of NK4 is restricted dorsally by the BMP antagonist Chordin, while the ventrally-expressed transcription factor Msx can alleviate the repressive effect of NK4, potentially allowing for the characteristic tripartite patterning of the papillae.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012334"},"PeriodicalIF":3.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The AF-2 domain of estrogen-related receptor interacts with PPRC1 to modulate larval epidermal marking in Bombyx mori.","authors":"Jinxin Wu, Die Liu, Haoran Xu, Lingqing Zeng, Ping Lin, Ping Zhao, Guanwang Shen","doi":"10.1371/journal.pgen.1012339","DOIUrl":"10.1371/journal.pgen.1012339","url":null,"abstract":"<p><p>Estrogen-related receptors (ERRs) have no natural ligands, vertebrate ERRs rely on their activation function-2 (AF-2) structural domain to recruit coactivators for transcriptional regulation. While metabolic regulation in insects differs significantly from that in vertebrates, it remains unclear whether the regulatory function of insect ERR requires coactivators. Using silkworms as the research subject, this study aims to analyze the molecular mechanisms of ERR-regulated metabolism in insects and refine the metabolic regulatory network. This study applied CRISPR/Cas9 gene editing technology to knock out the AF-2 domain of BmERR in the lepidopteran silkworms and examined its effects on functional role, associated interacting factors, and related physiological processes. Disruption of the BmERR AF-2 domain inhibited the expression of melanin metabolism-related genes BmTH, BmDDC, BmAA-NAT, Bmebony, and Bmtan, leading to the accumulation of tyrosine and dopa, thereby causing aberrant melanin metabolism and loss of epidermal markings. By contrast, BmERR overexpression enhanced the pathway, resulting in intensification of epidermal markings. The homologous gene of the ERR coactivator, BmPPRC1, showed highly consistent expression with BmERR in the epidermis. The immunofluorescence signal of BmPPRC1 was localized to the nucleus and highly overlapped with that of BmERR. BmPPRC1 interacts with the AF-2 domain of BmERR, and deletion of this region weakens the regulation of melanin metabolism-related genes in silkworm embryonic cells. The ERR function and mode of action are evolutionarily conserved, and its AF-2 structural domain binds equally well to the coactivator BmPPRC1, providing new perspectives for studying the modulability of insect mottle formation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012339"},"PeriodicalIF":3.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into Müllerian duct differentiation provided by single cell transcriptomics in the chicken embryo.","authors":"Juan Lan Tan, Adele Barugahare, Andrew Thomas Major, Craig Allen Smith","doi":"10.1371/journal.pgen.1012302","DOIUrl":"10.1371/journal.pgen.1012302","url":null,"abstract":"<p><p>In vertebrate embryos, Müllerian ducts give rise to the female reproductive tract. Here, we present a comprehensive analysis of Müllerian duct differentiation using single cell transcriptomics in the chicken embryo, a unique model for duct development. The data reveal greater cellular complexity of Müllerian duct differentiation than previously understood. Transcriptomic profiling of early formed Müllerian ducts identifies molecular signatures for the Müllerian duct Epithelium (MDE) and the Müllerian Duct Mesenchyme (MDM), the two principle compartments of the Müllerian duct. The MDE expresses PAX2, LHX1, WNT7, LGR5, PDGFA/D, and CDH1/2. The MDM is marked by WNT4, EMX2, POSTN, OSR1, VIM,DMRT and the EMT markers ZEB1/2. In the male, the regressing mesenchyme (MDM) has a unique molecular signature, expressing the transcription factors MSX1, MSX2, RUNX2, GATA5, DLX3 and DLX5, and the signaling regulators DKK4 and NRG1 (Neuregulin). Single cell transcript profiling of the regressing male mesenchyme identifies new genes implicated in duct regression, including the WNT antagonist, DKK4. DKK4, responds to Anti-Mullerian Hormone induction and can induce duct regression when ectopically expressed in females. The duct mesenchyme in the female follows a different fate, with a molecular signature comprising SMARCA2/ HMGA2/ZEB1/2/TWIST1/2/DMRT2 and persistent expression of FOXE1, OSR2 and HGF (Hepatocyte Growth Factor). Cell clusters in the developing female ducts reflects spatial pre-patterning of the duct prior to later regionalisation. In contrast to AMH-mediated bilateral Müllerian duct regression in males, female chicken embryos show an unusual pattern of left duct differentiation and contralateral right duct regression. We find that right female duct does not regress in the same manner as in males, being transcriptionally distinct and lacking a population of regressing mesenchyme, despite presumably being mediated by AMH, as in males.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012302"},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined lactate- and phosphate-dependent cytoplasmic acidification is associated with Mycobacterium tuberculosis growth arrest at acidic pH.","authors":"Adam P Kibiloski, Shelby J Dechow, Bassel J Abdalla, Heather M Murdoch, Anna D Tischler, Robert B Abramovitch","doi":"10.1371/journal.pgen.1012331","DOIUrl":"10.1371/journal.pgen.1012331","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (Mtb) cultured in minimal medium at acidic pH arrests growth when provided specific single carbon sources, including glycerol, propionate, and lactate, a phenomenon we refer to as acid growth arrest. To define the mechanisms of acid growth arrest on lactate, we selected transposon mutants that grew under these conditions. Five mutants carried insertions in phoT or pstC2, which encode components of a phosphate ABC transporter. Depleting phosphate restored Mtb growth in minimal medium supplemented with lactate at acidic pH, demonstrating that growth arrest on lactate depended on phosphate. The combination of lactate and phosphate at acidic pH acidified the cytoplasm to below pH 6.7, whereas the phoT mutant maintained a cytoplasmic pH > 7.2. Lactate slightly decreased membrane potential in a dose-dependent manner in wild-type Mtb, whereas the phoT mutant maintained a higher membrane potential. Transcriptional profiling identified a lactate-associated PMF stress signature, including upregulation of electron transport chain genes. Together, these findings associate lactate- and phosphate-dependent cytoplasmic acidification with proton motive force (PMF) stress and acid growth arrest. The phoT mutant grown in lactate at acidic pH upregulated the senX3/regX3 regulon. Using a regX3 mutant, we found that growth on lactate under low-phosphate conditions required regX3. We propose a model in which (1) acidic pH, lactate, and phosphate together modulate cytoplasmic pH homeostasis and are associated with PMF stress and acid growth arrest; and (2) low phosphate induces SenX3-RegX3 activity, which may alter cell-envelope physiology through ESX-5- and PE/PPE-dependent pathways and promote growth on lactate at acidic pH.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012331"},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZBED6 deficiency drives pathological cardiac hypertrophy through MEOX1-ERK1/2-dependent autophagy dysfunction.","authors":"Xiao Zhang, Xiaopeng Liu, Ruirui Pan, Huan Liu, Junying Xiao, Xiangkai Leng, Hongmei Zhang, Dengke Pan, Shengzhong Duan, Jiangwei Wu","doi":"10.1371/journal.pgen.1012329","DOIUrl":"10.1371/journal.pgen.1012329","url":null,"abstract":"<p><p>Pathological cardiac hypertrophy, a major risk factor for heart failure, is regulated by complex transcriptional networks. We previously identified the transcription factor ZBED6 as a key regulator for skeletal muscle hypertrophy, its role in the cardiac hypertrophy remains unexplored. Here, we report that ZBED6 is a key suppressor of pathological cardiac hypertrophy. ZBED6 is markedly reduced in myocardial tissues from patients with cardiac hypertrophy. ZBED6-deficient pigs exhibited cardiac hypertrophy with diastolic dysfunction. Integrative transcriptomic and ChIP-seq analyses identified MEOX1 as a direct negative target of ZBED6. Loss of ZBED6 upregulates MEOX1 transcription, which subsequently activated ERK1/2 signaling, leading to impaired autophagy-induced hypertrophy. Knockdown of MEOX1 reduced ERK1/2 phosphorylation and mitigated cardiomyocyte hypertrophy induced by ZBED6 deficiency. Similarly, pharmacological inhibition of ERK1/2 restored autophagy and alleviated hypertrophy in ZBED6-depleted cardiomyocytes. Collectively, these findings define a previously unrecognized ZBED6-MEOX1-ERK1/2 axis that critically regulates cardiac hypertrophy and represents a potential therapeutic target.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012329"},"PeriodicalIF":3.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin stability safeguards mitochondrial homeostasis and restrains TORC1 signaling.","authors":"Vinoth Sigamani, Mohd Yousuf, Daniel L Johnson, Brian D Strahl, R Nicholas Laribee","doi":"10.1371/journal.pgen.1012330","DOIUrl":"10.1371/journal.pgen.1012330","url":null,"abstract":"<p><p>Chromatin is dynamically regulated in response to nutrient flux to promote the transcriptional changes needed for adaptation. The mechanistic target of rapamycin complex 1 (yeast TORC1) kinase integrates nutrient signaling with chromatin regulation, yet whether chromatin signals back to regulate TORC1 remains unclear. We find that a histone H3 lysine 37 to alanine (H3K37A) mutant predicted to disrupt a histone-DNA contact promotes histone degradation, hyperactivates TORC1, and causes cytotoxicity upon TORC1 inhibition. This cytotoxicity is specific to H3K37A, since chromatin instability in wild-type histone H3 (H3WT) cells reduces histone abundance and hyperactivates TORC1 without cytotoxicity upon TORC1 inhibition. Combining H3K37A with these chromatin stability mutants exacerbates histone loss, TORC1 hyperactivity, and lethality during TORC1 inhibition. Transcriptome analysis indicates H3K37A deregulates mitochondrial retrograde signaling, which is exacerbated upon TORC1 inhibition and becomes cytotoxic due in part to defective mitochondrial import of an OXPHOS subunit. Retrograde inactivation, or neutralization of reactive oxygen species (ROS) prevents this toxicity. These findings identify chromatin stability as an upstream restraint on TORC1 signaling, revealing bidirectional communication between chromatin and a major nutrient-responsive pathway. They further show H3K37 has an additional functionality that prevents mitochondrial dysregulation during metabolic stress adaptation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012330"},"PeriodicalIF":3.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat stress promotes GTBP-1 association with perinuclear P-bodies in the C. elegans germline.","authors":"Diya Zang, Yifan Jing, Xinya Huang, Yan Kuang, Jiewei Cheng, Wenkai Wang, Demin Xu, Chengming Zhu, Di Chen, Zhongying Zhao, Xuezhu Feng, Shouhong Guang","doi":"10.1371/journal.pgen.1012336","DOIUrl":"10.1371/journal.pgen.1012336","url":null,"abstract":"<p><p>Stress granules (SGs) are dynamic ribonucleoprotein condensates that enable cells to adapt to environmental stress, yet their functions and regulation in the germline remain incompletely understood. Here, we characterize GTBP-1, the Caenorhabditis elegans homolog of human G3BP1, and investigate its role in heat stress responses and reproductive homeostasis. gtbp-1 mutants exhibit temperature-dependent reproductive phenotypes. Under normal growth conditions, GTBP-1 is diffusely distributed in the cytoplasm, whereas heat stress induces the formation of prominent GTBP-1 granules in the germline. Domain analysis revealed that the NTF2 domain is required for heat stress-induced GTBP-1 enrichment in granules, while the IDR, RRM, and RGG domains contribute to GTBP-1 granule dynamics. Among the known germ granule compartments, GTBP-1 granules showed the strongest association with P-bodies, and disruption of P-body components markedly reduces GTBP-1 enrichment. RNAi-based candidate screening identified PQN-59, LAF-1, and SMO-1 as regulators of GTBP-1 enrichment, while a forward genetic screen revealed that loss of the mTOR effector RSKS-1 suppresses the fertility defect of gtbp-1 mutants and alters heat stress-induced GTBP-1 enrichment. Together, these findings identify a role for GTBP-1 in temperature-dependent reproductive homeostasis and reveal an association between heat stress-induced GTBP-1 granules and P-bodies in C. elegans.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012336"},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPC: An expressive and tractable deep generative model for genetic variation data.","authors":"Prateek Anand, Anji Liu, Meihua Dang, Boyang Fu, Xinzhu Wei, Guy Van den Broeck, Sriram Sankararaman","doi":"10.1371/journal.pgen.1012321","DOIUrl":"10.1371/journal.pgen.1012321","url":null,"abstract":"<p><p>Generative models play an important role in population genetics, being used to generate artificial genomes (AGs) that help benchmark methods, test evolutionary hypotheses, and construct reference panels for imputation while working around data-sharing restrictions. Existing generative models of genetic variation, however, struggle to faithfully express dependencies in the data while retaining tractability and preserving privacy. We introduce Genetic Probabilistic Circuits (GPC), a deep generative model for genetic variation data based on hidden Chow-Liu trees represented as probabilistic circuits. GPC generalizes traditional hidden Markov models by allowing arbitrary tree structures over latent variables, enabling it to capture long-range dependencies among SNPs. GPC is tractable, supporting exact computation of marginal and conditional probabilities that enables both AG generation and direct genotype imputation (avoiding the need for simulating AGs). We show that GPC generates AGs that accurately reproduce population structure and linkage disequilibrium patterns across a range of length scales. Compared to other deep generative approaches, GPC consistently improves imputation accuracy, with particularly strong gains for low-frequency variants and in populations that are not well-represented in public reference panels. Finally, we show that GPC better preserves privacy of the training data, thereby providing a practical framework for AG generation in settings with limited data access.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012321"},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic architecture of basal heart rate and its modulation by dietary salt in Drosophila melanogaster.","authors":"Gulnur Ipek Erdemli, Murat Yilmaz, Alp Mete Ummet, Fatih Akdemir, Ergi Deniz Ozsoy","doi":"10.1371/journal.pgen.1012313","DOIUrl":"https://doi.org/10.1371/journal.pgen.1012313","url":null,"abstract":"<p><p>Heart rate (HR) is a complex quantitative phenotype that is influenced by both genetic and environmental factors, and it is a critical factor in the regulation of cardiac physiology. Despite the discovery of numerous genes associated with HR variation in humans and other organisms, the mechanisms by which these genes interact to affect HR changes in natural environments and their responses to environmental stressors remain incompletely understood. In this study, the genetic basis of basal HR and the response to salt stress were examined using the Drosophila Genetic Reference Panel (DGRP). The 154 DGRP lines exhibited moderate broad-sense heritability and substantial genetic variation in HR measurements during the third larval stage, with males and females analyzed separately, under both standard and 0.1% NaCl-containing medium conditions. The mixed-effects model revealed that the interaction between genotype and environment significantly influences HR. Genome-wide association analysis identified gene variants associated with critical biological processes such as ion transport, cardiac development, protein homeostasis, metabolism, and stress response. The identification of different genes under standard and saline (NaCl-supplemented) conditions suggests that environmental stress unlocks cryptic genetic variation. Candidate genes were tested using heart-specific GAL4 drivers in RNAi experiments, and a considerable number of these genes were found to significantly affect HR based on sex and the environment. These findings reveal that HR variation is strongly shaped by genotype-by-environment interactions and sex-specific genetic effects, with distinct sets of genes contributing under basal and stress conditions. The identification of environment-dependent genetic architectures suggests that salt stress can expose cryptic genetic variation influencing cardiac function. By integrating genome-wide association analyses with targeted RNAi-based functional validation, this study provides a framework for linking natural genetic variation to physiological phenotypes in a context-dependent manner.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012313"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation.","authors":"Rochelle E Yap, Felicia Ebot-Ojong, Abigail J Ameri-Solanky, Zachary A Lewis","doi":"10.1371/journal.pgen.1012327","DOIUrl":"10.1371/journal.pgen.1012327","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 10","pages":"e1012327"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}