{"doi":"10.1371/journal.pbio.2004986","title":"Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids","abstract":null,"journal":"PLOS Biology","year":2018,"id":627108,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1622613,"name":"Michael J. G. Milevskiy","orcid":null,"position":1,"is_corresponding":false},{"id":1622614,"name":"Rachel M. Joyce","orcid":null,"position":2,"is_corresponding":false},{"id":1622615,"name":"Johanna F. Dekkers","orcid":null,"position":3,"is_corresponding":false},{"id":1622616,"name":"Paul R. Jamieson","orcid":null,"position":4,"is_corresponding":false},{"id":1014102,"name":"Bhupinder Pal","orcid":"0000-0002-3684-4331","position":5,"is_corresponding":false},{"id":1070621,"name":"Caleb A. Dawson","orcid":"0000-0002-6835-6930","position":6,"is_corresponding":false},{"id":50998,"name":"Yifang Hu","orcid":"0000-0001-8200-0052","position":7,"is_corresponding":false},{"id":805363,"name":"Stuart H. Orkin","orcid":"0000-0002-3523-7687","position":8,"is_corresponding":false},{"id":285439,"name":"Warren S. Alexander","orcid":"0000-0002-1824-7701","position":9,"is_corresponding":false},{"id":287592,"name":"Geoffrey J. Lindeman","orcid":"0000-0001-9386-2416","position":10,"is_corresponding":false},{"id":36695,"name":"Gordon K. Smyth","orcid":"0000-0001-9221-2892","position":11,"is_corresponding":false},{"id":1622617,"name":"Jane E. Visvader","orcid":null,"position":12,"is_corresponding":false},{"id":1622612,"name":"Ewa M. Michalak","orcid":"0000-0002-5772-2122","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids","abstract":"Distinct transcriptional states are maintained through organization of chromatin, resulting from the sum of numerous repressive and active histone modifications, into tightly packaged heterochromatin versus more accessible euchromatin. Polycomb repressive complex 2 (PRC2) is the main mammalian complex responsible for histone 3 lysine 27 trimethylation (H3K27me3) and is integral to chromatin organization. Using in vitro and in vivo studies, we show that deletion of Suz12, a core component of all PRC2 complexes, results in loss of H3K27me3 and H3K27 dimethylation (H3K27me2), completely blocks normal mammary gland development, and profoundly curtails progenitor activity in 3D organoid cultures. Through the application of mammary organoids to bypass the severe phenotype associated with Suz12 loss in vivo, we have explored gene expression and chromatin structure in wild-type and Suz12-deleted basal-derived organoids. Analysis of organoids led to the identification of lineage-specific changes in gene expression and chromatin structure, inferring cell type-specific PRC2-mediated gene silencing of the chromatin state. These expression changes were accompanied by cell cycle arrest but not lineage infidelity. Together, these data indicate that canonical PRC2 function is essential for development of the mammary gland through the repression of alternate transcription programs and maintenance of chromatin states.","is_dataset_classified":null,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30080881","pmcid":"PMC6095611","openalex_id":"https://openalex.org/W2887480824","authors":[],"funders":[{"funder_name":"EPA","grant_id":"EP-C-15-002","title":null},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1016701","title":"Apoptosis and Stem Cells in Cancer Development and Therapy"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1054618","title":"Computational and statistical bioinformatics for medical “omics”"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1113577","title":"Regulation of Haemopoietic and Immune Cells in Health and Disease"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1024852","title":"Exploring the role of microRNA and target processing variability in cardiac hypertrophy"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1058344","title":"Molecular Regulation of Haematopoiesis in Health and Disease"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1086727","title":"Elucidating the in vivo role of the pro-survival gene Mcl-1 in mammary gland development and breast cancer"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1078730","title":"Research Fellowship"}],"total_grants":8,"fwci":0.6597,"citation_percentile":0.66966533,"influential_citations":0,"citation_trend":[{"year":2019,"count":2},{"year":2020,"count":4},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2004986&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2004986&type=printable","host_type":"GOLD"},{"url":"https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2004986&type=printable","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pbio.2004986","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30080881","host_type":"repository"},{"url":"http://hdl.handle.net/11343/271043","host_type":"repository"},{"url":"https://doaj.org/article/2db4d265c7794554b6a813e67f3a5cdf","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC6095611","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Canonical_PRC2_function_is_essential_for_mammary_gland_development_and_affects_chromatin_compaction_in_mammary_organoids/6936524","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6095611","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6095611","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6095611?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pbio.2004986","host_type":""},{"url":"https://api.library.uq.edu.au/view/UQ:ea283b6","host_type":""},{"url":"https://espace.library.uq.edu.au/view/UQ:ea283b6","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pbio.2004986","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pbio.2004986","host_type":""}],"fields_of_study":["Epigenetics and DNA Methylation","Genomics and Chromatin Dynamics","Cancer Cells and Metastasis","Biology","Medicine","0301 basic medicine","03 medical and health sciences","Animals","Chromatin","Enhancer of Zeste Homolog 2 Protein","Female","Heterochromatin","Histone Code","Histones","Lysine","Mammary Glands, Animal","Methylation","Mice","Polycomb Repressive Complex 2","Polycomb-Group Proteins","Primary Cell Culture","Protein Processing, Post-Translational"],"mesh_terms":["Enhancer of Zeste Homolog 2 Protein","Animals","Chromatin","Female","Heterochromatin","Histones","Lysine","Mammary Glands, Animal","Methylation","Protein Processing, Post-Translational","Histone Code","Mice","Primary Cell Culture","Polycomb-Group Proteins","Polycomb Repressive Complex 2"],"keywords":["Chromatin","Biology","PRC2","Bivalent chromatin","Cell biology","Histone","Chromatin remodeling","Histone H3","Organoid","Histone-modifying enzymes","Epigenomics","DNA methylation","Genetics","Gene expression","Gene","2800 Neuroscience","570","QH301-705.5","Primary Cell Culture","Polycomb-Group Proteins","Methylation","Histones","1100 Agricultural and Biological Sciences","Mice","Mammary Glands, Animal","1300 Biochemistry, Genetics and Molecular Biology","Heterochromatin","Animals","Enhancer of Zeste Homolog 2 Protein","Biology (General)","Lysine","Polycomb Repressive Complex 2","500","2400 Immunology and Microbiology","Histone Code","Female","Protein Processing, Post-Translational","Research 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