{"doi":"10.1073/pnas.2220613120","title":"PGE <sub>2</sub> alters chromatin through H2A.Z-variant enhancer nucleosome modification to promote hematopoietic stem cell fate","abstract":"Prostaglandin E2 (PGE 2 ) and 16,16-dimethyl-PGE 2 (dmPGE 2 ) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies [C. Cutler et al. Blood 122 , 3074–3081(2013); W. Goessling et al. Cell Stem Cell 8 , 445–458 (2011); W. Goessling et al. Cell 136 , 1136–1147 (2009)]. Here, we report that PGE 2 -induced changes in chromatin at enhancer regions through histone-variant H2A.Z permit acute inflammatory gene induction to promote HSPC fate. We found that dmPGE 2 -inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes permissive of CREB transcription factor (TF) binding. CREB binding to enhancer nucleosomes following dmPGE 2 stimulation is concomitant with deposition of histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone-variant nucleosomes retained within inducible enhancers facilitate TF binding. Histone-variant acetylation by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism through which inflammatory mediators, such as dmPGE 2 , lead to acute transcriptional changes and modify HSPC behavior to improve stem cell transplantation.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":329870,"datarank":0.5210654422024907,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.08750967851806601,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.08750967851806601,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":16,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":355052,"name":"Avik Choudhuri","orcid":null,"position":1,"is_corresponding":false},{"id":90706,"name":"Meera Prasad","orcid":null,"position":2,"is_corresponding":false},{"id":702367,"name":"Brejnev Muhire","orcid":"0000-0002-5594-1348","position":3,"is_corresponding":false},{"id":71895,"name":"Eva M. Fast","orcid":"0000-0002-4261-5244","position":4,"is_corresponding":false},{"id":703339,"name":"Margot E. Manning","orcid":"0000-0002-2933-0789","position":5,"is_corresponding":false},{"id":1053540,"name":"Jodi D. Weiss","orcid":null,"position":6,"is_corresponding":false},{"id":1053073,"name":"Michelle Koh","orcid":"0000-0001-5044-7845","position":7,"is_corresponding":false},{"id":354451,"name":"Song Yang","orcid":"0000-0002-3064-3141","position":8,"is_corresponding":false},{"id":23407,"name":"Robert E. Kingston","orcid":"0000-0003-3628-4335","position":9,"is_corresponding":false},{"id":23418,"name":"Michael Tolstorukov","orcid":"0000-0002-9134-8808","position":10,"is_corresponding":false},{"id":3646,"name":"Hans Clevers","orcid":"0000-0002-3077-5582","position":11,"is_corresponding":false},{"id":49576,"name":"Leonard I. Zon","orcid":"0000-0003-0860-926X","position":12,"is_corresponding":false},{"id":355055,"name":"Audrey Sporrij","orcid":null,"position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:09:05.843139Z","pmid":"37126722","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":[]}