{"doi":"10.1101/2022.12.12.519332","title":"High Density Domain-Focused CRISPR Screens Reveal Novel Epigenetic Regulators of <i>HOX/MEIS</i> Activation in Acute Myeloid Leukemia","abstract":"ABSTRACT Aberrant expression of stem-cell-associated genes is a common feature in acute myeloid leukemia (AML) and is linked to leukemic self-renewal and therapy resistance. Using AF10-rearranged leukemia as a prototypical example displaying a recurrent “ stemness ” network activated in AML, we screened for chromatin regulators that sustain aberrant activation of these networks. We deployed a CRISPR-Cas9 screen with a bespoke domain-focused library and identified several novel chromatin-modifying complexes as regulators of the TALE domain transcription factor MEIS1, a key leukemia stem cell (LSC)-associated gene. CRISPR droplet sequencing revealed that many of these MEIS1 regulators coordinately controlled the transcription of several AML oncogenes. In particular, we identified a novel role for the Tudor-domain containing chromatin reader protein SGF29 in the transcription of key AML oncogenes. Furthermore, SGF29 deletion impaired leukemogenesis in models representative of multiple AML subtypes. Our studies reveal a novel role for SGF29 as a non-oncogenic dependency in AML and identify the SGF29 Tudor domain as an attractive target for drug discovery.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":305131,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":567677,"name":"Anagha Deshpande","orcid":"0000-0002-5653-2837","position":1,"is_corresponding":false},{"id":999039,"name":"Marlenne Perales","orcid":null,"position":2,"is_corresponding":false},{"id":355021,"name":"Ping Xiang","orcid":null,"position":3,"is_corresponding":false},{"id":695226,"name":"Rabi Murad","orcid":"0009-0004-5297-8307","position":4,"is_corresponding":false},{"id":24511,"name":"Anna Minkina","orcid":"0000-0002-7989-4478","position":5,"is_corresponding":false},{"id":549949,"name":"Neil Robertson","orcid":"0000-0002-9509-1157","position":6,"is_corresponding":false},{"id":440002,"name":"Fiorella Schischlik","orcid":"0000-0003-4299-7657","position":7,"is_corresponding":false},{"id":549953,"name":"Xue Lei","orcid":"0000-0001-9647-3782","position":8,"is_corresponding":false},{"id":998622,"name":"Younguk Sun","orcid":"0000-0002-1246-2558","position":9,"is_corresponding":false},{"id":253762,"name":"Adam Brown","orcid":"0000-0002-9122-4960","position":10,"is_corresponding":false},{"id":999040,"name":"Diana Amend","orcid":null,"position":11,"is_corresponding":false},{"id":567680,"name":"Irmela Jeremias","orcid":"0000-0003-1773-7677","position":12,"is_corresponding":false},{"id":54229,"name":"John G. Doench","orcid":"0000-0002-3707-9889","position":13,"is_corresponding":false},{"id":515135,"name":"R. Keith Humphries","orcid":"0000-0003-0540-7005","position":14,"is_corresponding":false},{"id":36510,"name":"Jay Shendure","orcid":"0000-0002-1516-1865","position":16,"is_corresponding":false},{"id":62764,"name":"Prashant Mali","orcid":"0000-0002-3383-1287","position":17,"is_corresponding":false},{"id":227838,"name":"Peter D. Adams","orcid":"0000-0002-0684-1770","position":18,"is_corresponding":false},{"id":259809,"name":"Aniruddha J. Deshpande","orcid":"0000-0002-5240-9356","position":19,"is_corresponding":false},{"id":567678,"name":"Karina Barbosa","orcid":"0000-0002-6233-3332","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T00:32:37.185846Z","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":[]}