{"doi":"10.1093/nar/gkab737","title":"HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis","abstract":"The activity of hematopoietic factor GATA-1 is modulated through p300/CBP-mediated acetylation and FOG-1 mediated indirect interaction with HDAC1/2 containing NuRD complex. Although GATA-1 acetylation is implicated in GATA-1 activation, the role of deacetylation is not studied. Here, we found that the FOG-1/NuRD does not deacetylate GATA-1. However, HDAC1/2 can directly bind and deacetylate GATA-1. Two arginine residues within the GATA-1 linker region mediates direct interaction with HDAC1. The arginine to alanine mutation (2RA) blocks GATA-1 deacetylation and fails to induce erythroid differentiation. Gene expression profiling and ChIP-seq analysis further demonstrate the importance of GATA-1 deacetylation for gene activation and chromatin recruitment. GATA-12RA knock-in (KI) mice suffer mild anemia and thrombocytopenia with accumulation of immature erythrocytes and megakaryocytes in bone marrow and spleen. Single cell RNA-seq analysis of Lin- cKit+ (LK) cells further reveal a profound change in cell subpopulations and signature gene expression patterns in HSC, myeloid progenitors, and erythroid/megakaryocyte clusters in KI mice. Thus, GATA-1 deacetylation and its interaction with HDAC1 modulates GATA-1 chromatin binding and transcriptional activity that control erythroid/megakaryocyte commitment and differentiation.","journal":"Nucleic Acids Research","year":2021,"id":189346,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":751919,"name":"Jennifer Yang","orcid":"0000-0001-8149-5161","position":1,"is_corresponding":false},{"id":337658,"name":"Min Young Kim","orcid":"0000-0002-7001-3670","position":2,"is_corresponding":false},{"id":335205,"name":"Huacheng Luo","orcid":"0000-0002-5844-8890","position":3,"is_corresponding":false},{"id":751920,"name":"Nicholas Cesari","orcid":"0000-0001-8851-3991","position":4,"is_corresponding":false},{"id":298821,"name":"Tao Yang","orcid":"0000-0002-4182-9793","position":5,"is_corresponding":false},{"id":455294,"name":"John Strouboulis","orcid":"0000-0002-6133-2872","position":6,"is_corresponding":false},{"id":294082,"name":"Jiwang Zhang","orcid":"0000-0003-4309-2892","position":7,"is_corresponding":false},{"id":19594,"name":"Ross C. Hardison","orcid":"0000-0003-4084-7516","position":8,"is_corresponding":false},{"id":335212,"name":"Suming Huang","orcid":"0000-0002-4788-2085","position":9,"is_corresponding":false},{"id":337660,"name":"Yi Qiu","orcid":"0000-0002-3282-6072","position":10,"is_corresponding":false},{"id":337659,"name":"Bowen Yan","orcid":"0000-0003-4730-6763","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:49:18.604374Z","pmid":"34450641","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":[]}