{"doi":"10.1101/2021.07.19.452879","title":"A dynamic and combinatorial histone code drives malaria parasite asexual and sexual development","abstract":"Abstract A ‘histone code’ defines system-level crosstalk between histone post-translational modifications (PTMs) to induce specific biological outcomes. Proteome-scale information of co-existing PTM across the entire chromatin landscape of the malaria parasite, Plasmodium falciparum, was lacking. Here, we used advanced quantitative middle-down proteomics to identify combinations of PTMs in both the proliferative, asexual stages and transmissible, sexual gametocyte stages of P. falciparum . We provide an updated, high-resolution compendium of 72 PTMs on H3 and H3.3, of which 30 are novel to the parasite. Co-existing PTMs with unique stage distinction was identified, indicating a dynamic and complex histone code with increased connectivity of novel PTMs seen in gametocytes. Chromatin proteomics of a gametocyte-specific combination, H3R17me2K18acK23ac, identified a SAGA-like effector complex (including the transcription factor AP2-G2) tied to this combination to regulate gene expression in mature gametocytes. Ultimately, this study unveils previously undiscovered histone PTMs and their functional relationship with co-existing partners. These results highlight that investigating chromatin regulation in the parasite using single histone PTM assays might overlook higher order gene regulation for distinct proliferation and differentiation processes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221251,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8529,"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":269895,"name":"Mariel Coradin","orcid":"0000-0003-3560-4384","position":1,"is_corresponding":false},{"id":395036,"name":"Mariel Mendoza","orcid":"0000-0003-2072-4914","position":2,"is_corresponding":false},{"id":395745,"name":"Janette Reader","orcid":"0000-0001-9026-0583","position":3,"is_corresponding":false},{"id":247704,"name":"Simone Sidoli","orcid":"0000-0001-9073-6641","position":4,"is_corresponding":false},{"id":227837,"name":"Benjamin A. García","orcid":"0000-0002-2306-1207","position":5,"is_corresponding":false},{"id":395748,"name":"Lyn‐Marié Birkholtz","orcid":"0000-0001-5888-2905","position":6,"is_corresponding":false},{"id":821250,"name":"Hilde von Grüning","orcid":"0000-0001-6089-3742","position":0,"is_corresponding":true}],"reference_count":127,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:55.215284Z","pmid":null,"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":[]}