{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE292nnn/GSE292237/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292237"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"H2AK119ub1 counteracts MLL2 functions to direct heritable H3K27me3 formation in mouse oocytes","description":"Polycomb group (PcG) and Trithorax group (TrxG) family proteins form repressive and permissive states of chromatin, respectively, to regulate developmental genes. They counteract with each other at bivalent chromatin marked by Polycomb repressive complex 2 (PRC2)-deposited H3K27me3, PRC1-deposited H2AK119ub1, and MLL2-deposited H3K4me3. However, it is unknown how they counteract to form bivalent chromatin in mammalian development. Here, by using mouse oocytes as a model in which bivalent chromatin and H3K27me3-dependent noncanonical imprinting are established during the non-dividing growth phase of oogenesis, we show that H3K27me3 is deposited at H3K4me3-premarked promoters in an H2AK119ub1-dependent manner. We find that H2AK119ub1 deficiency causes transcriptional derepression of bivalent genes and H3K36me2/3 deposition across the gene bodies, which are concurrent with loss of H3K27me3 at both promoters and gene bodies in Pcgf1/6 double KO oocytes. Importantly, upon combinatorial deficiency of H2AK119ub1 and promoter H3K4me3, both transcriptional repression and H3K27me3 deposition are substantially restored in Pcgf1/6/Mll2 TKO oocytes. This leads to restoration of maternal allele silencing of Sfmbt2, a noncanonical imprinted gene essential for placental development, and consequently normalization of placental growth in the offspring. Taken together, we propose that vPRC1-mediated H2AK119ub1 antagonizes MLL2 functions to confer intergenerationally heritable H3K27me3 during oogenesis. This study uncovers how PcG and TrxG counteraction shapes the maternal epigenome for the next generation development.","dates":{"publication":"2026/04/01"},"accession":"GSE292237","cross_references":{"GSM":["GSM8853898","GSM8853910","GSM8853899","GSM8853911","GSM8853912","GSM8853913","GSM8853914","GSM8853915","GSM8853916","GSM8853890","GSM8853891","GSM8853892","GSM8853893","GSM8853894","GSM8853895","GSM8853896","GSM8853897","GSM8853906","GSM8853907","GSM8853908","GSM8853909","GSM8853887","GSM8853920","GSM8853921","GSM8853888","GSM8853889","GSM8853922","GSM8853900","GSM8853901","GSM8853923","GSM8853924","GSM8853902","GSM8853925","GSM8853903","GSM8853904","GSM8853926","GSM8853927","GSM8853905","GSM8853885","GSM8853886","GSM8853917","GSM8853918","GSM8853919"],"GPL":["19057"],"GSE":["292237"],"taxon":["Mus musculus"]}}