[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-407533-105":59,"doc-detail-407533-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","maternal-histone-methyltransferases-antagonistically-regulate-autosomal-random-monoallelic-expression-armae-in-c-elegans","Maternal histone methyltransferases antagonistically regulate autosomal random monoallelic expression (aRMAE) in C. elegans","","Probabilistic autosomal random monoallelic expression (aRMAE) can silence individual alleles and generate unique phenotypes even among genetic clones. Using Caenorhabditis elegans, the study defines a developmental genetic pathway controlling aRMAE in whole tissues. Maternal H3K9 HMT SET-25 acts with HPL-2/HP1 and LIN-61/L3MBTL2 to randomly silence alleles in intestinal progenitor E-cells, while MET-2 antagonizes this process. Both catalytic SET domains are required, and regulation yields persistent somatic monoallelic patterns that are not heritable across generations.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/maternal-histone-methyltransferases-antagonistically-regulate-autosomal-random-monoallelic-expression-armae-in-c-elegans/407533/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/maternal-histone-methyltransferases-antagonistically-regulate-autosomal-random-monoallelic-expression-armae-in-c-elegans/407533.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does aRMAE explain in organisms with identical genetics?","Question",{"text":112,"@type":113},"aRMAE probabilistically silences individual autosomal alleles, creating phenotypic differences between genetically clonal individuals.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which maternal enzymes control monoallelic expression in C. elegans?",{"text":117,"@type":113},"SET-25 (H3K9 HMT) works with HPL-2/HP1 and LIN-61/L3MBTL2 to promote random allele silencing, while MET-2 (another maternal H3K9 HMT) antagonizes monoallelic expression.",{"name":119,"@type":110,"acceptedAnswer":120},"Are the monoallelic expression patterns heritable across generations?",{"text":121,"@type":113},"The patterns are persistent but not heritable between generations.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},407533,1792223688,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Article [https://doi.org/10.1038/s41467-025-66501-5](https://doi.org/10.1038/s41467-025-66501-5)  \nMaternal histone methyltransferases antagonistically regulate autosomal random monoallelic expression(aRMAE)inC. elegans  \nReceived: 26 March 2024  \n\n| Accepted: 6 November 2025 |\n| --- |\n| |\n| Check for updates |\n\nBryan Sands, Soo R. Yun, Junko Oshima & Alexander R. Mendenhall   \nUndefined epigenetic programs act to probabilistically silence individual autosomal alleles, generating unique individuals, even from genetic clones. This random monoallelic expression can explain variation in traits and diseases that differences in genes and environments cannot. Here, we developed the nematode Caenorhabditis elegans to study monoallelic expression in whole tissues, and defined a developmental genetic regulation pathway. We found maternal H3K9 histone methyltransferase (HMT) SET-25/SUV39/G9a works with HPL-2/HP1 and LIN-61/L3MBTL2 to randomly silence alleles in the intestinal progenitor E-cell of 8-cell embryos to cause monoallelic expression. SET-25 was antagonized by another maternal H3K9 HMT, MET-2/SETDB1, which works with LIN-65/ATF7IP and ARLE-14/ARL14EP to prevent monoallelic expression. The HMT catalytic SET domains of both MET-2 and SET-25 were required for regulating monoallelic expression. Our data support a model wherein SET-25 and MET-2 regulate histones during development to generate patterns of somatic monoallelic expression that are persistent but not heritable.  \nWhen accounting for variation in traits, scientists bin variation into genes, environment, and a third component that accounts for biological variation that is considered nongenetic and nonenvironmental1. In model animal research, it is possible to hold genes and environments as constants, so the remaining variation in traits accounts for this nongenetic, nonenvironmental variation, which can be substantial2. Terms like incomplete penetrance and variable expressivity were coined to explain the observed variation in mutant phenotypes in isogenic populations of flies in homogeneous environments3–5. This intrinsic variation in discrete or complex traits can manifest through intrinsic variation in gene expression6,7, including through the endogenous silencing of genes, or even through the silencing of individual alleles8–10. This can account for incomplete penetrance, missing heritability, and nongenetic, nonenvironmental variation in complex traits, including the manifestation of chronic diseases. We refer to this probabilistic epigenetic silencing of alleles as autosomal random monoallelic expression (aRMAE), reviewed in refs. 8–10.  \nMonoallelic expression in humans  \naRMAE is widespread11 and consequential, but not entirely understood8–10. Since it is propagated through tissues, it has been detectable with both bulk RNA-seq12,13 and ChIP-seq14,15. Recent analysis of GTEX RNA-seq data has shown that genes with aRMAE potential are overwhelmingly enriched for effects on aging and chronic disease like cancer13. Moreover, aRMAE operates on a continuum, from fully monoallelic to biallelic, and the silencing of alleles is persistent, but not heritable between generations9,16.  \nMonoallelic expression affects human genetic disease and cancer. There are several cases of monoallelic expression affecting thepenetrance of genetic disease, cited in these reviews8–10,17. One example is a case study of a family that harbored a dominantnegative mutation in PIT118. In the three heterozygous individuals that harbored the dominant-negative disease allele (grandmother, father, and daughter), only the daughter was affected by disease. Analysis of RNA showed that the pathological disease allele was silenced in the disease-free family members (grandmother and  \nDepartment of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, USA. e-mail: [alexworm@uw.edu](alexworm@uw.edu)  \nFig. 1 | MET-2 negatively regulates monoallelic expression. a schematic ","cbCaidxhfs18JQv2","https://ap.wps.com/l/cbCaidxhfs18JQv2","pdf",3119064,16,"English","# Maternal histone methyltransferases antagonistically regulate aRMAE in C. elegans\n## aRMAE as probabilistic epigenetic silencing\n## aRMAE in human monoallelic expression and disease\n## Monoallelic expression affecting penetrance and cancer\n## The variable onset of genetic disease","[{\"question\":\"What does aRMAE explain in organisms with identical genetics?\",\"answer\":\"aRMAE probabilistically silences individual autosomal alleles, creating phenotypic differences between genetically clonal individuals.\"},{\"question\":\"Which maternal enzymes control monoallelic expression in C. elegans?\",\"answer\":\"SET-25 (H3K9 HMT) works with HPL-2/HP1 and LIN-61/L3MBTL2 to promote random allele silencing, while MET-2 (another maternal H3K9 HMT) antagonizes monoallelic expression.\"},{\"question\":\"Are the monoallelic expression patterns heritable across generations?\",\"answer\":\"The patterns are persistent but not heritable between generations.\"}]","Maternal histone methyltransferases antagonistically regulate autosomal random monoallelic expression (aRMAE) in C. elegans | PDF",1790574477]