{"doi":"10.1126/sciadv.aaz6477","title":"EED-mediated histone methylation is critical for CNS myelination and remyelination by inhibiting WNT, BMP, and senescence pathways","abstract":"Mutations in the polycomb repressive complex 2 (PRC2) can cause Weaver-like syndrome, wherein a patient cohort exhibits abnormal white matter; however, PRC2 functions in CNS myelination and regeneration remain elusive. We show here that H3K27me3, the PRC2 catalytic product, increases during oligodendrocyte maturation. Depletion of embryonic ectoderm development (EED), a core PRC2 subunit, reduces differentiation of oligodendrocyte progenitors (OPCs), and causes an OPC-to-astrocyte fate switch in a region-specific manner. Although dispensable for myelin maintenance, EED is critical for oligodendrocyte remyelination. Genomic occupancy and transcriptomic analyses indicate that EED establishes a chromatin landscape that selectively represses inhibitory WNT and bone morphogenetic protein (BMP) signaling, and senescence-associated programs. Blocking WNT or BMP pathways partially restores differentiation defects in EED-deficient OPCs. Thus, our findings reveal that EED/PRC2 is a crucial epigenetic programmer of CNS myelination and repair, while demonstrating a spatiotemporal-specific role of PRC2-mediated chromatin silencing in shaping oligodendrocyte identity and lineage plasticity.","journal":"Science Advances","year":2020,"id":91491,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458431,"name":"Lijun Yang","orcid":"0000-0001-5812-0118","position":1,"is_corresponding":false},{"id":233607,"name":"Chen Dong","orcid":"0000-0002-5405-5715","position":2,"is_corresponding":false},{"id":458432,"name":"Jincheng Wang","orcid":"0000-0002-3676-0779","position":3,"is_corresponding":false},{"id":460017,"name":"Lingli Xu","orcid":null,"position":4,"is_corresponding":false},{"id":460018,"name":"Yueping Qiu","orcid":null,"position":5,"is_corresponding":false},{"id":458433,"name":"Qinjie Weng","orcid":"0000-0001-8026-0109","position":6,"is_corresponding":false},{"id":309257,"name":"Chuntao Zhao","orcid":"0000-0002-2226-3827","position":7,"is_corresponding":false},{"id":458434,"name":"Mei Xin","orcid":"0000-0002-5732-7501","position":8,"is_corresponding":false},{"id":263829,"name":"Q. Richard Lu","orcid":"0000-0001-6846-9014","position":9,"is_corresponding":false},{"id":353665,"name":"Jiajia Wang","orcid":"0000-0002-0897-8033","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T22:29:21.932251Z","pmid":"32851157","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}