{"doi":"10.1016/j.xgen.2022.100119","title":"Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors","abstract":"Repeat elements can be dysregulated at a genome-wide scale in human diseases. For example, in Ewing sarcoma, hundreds of inert GGAA repeats can be converted into active enhancers when bound by EWS-FLI1. Here we show that fusions between EWS and GGAA-repeat-targeted engineered zinc finger arrays (ZFAs) can function at least as efficiently as EWS-FLI1 for converting hundreds of GGAA repeats into active enhancers in a Ewing sarcoma precursor cell model. Furthermore, a fusion of a KRAB domain to a ZFA can silence GGAA microsatellite enhancers genome wide in Ewing sarcoma cells, thereby reducing expression of EWS-FLI1-activated genes. Remarkably, this KRAB-ZFA fusion showed selective toxicity against Ewing sarcoma cells compared with non-Ewing cancer cells, consistent with its Ewing sarcoma-specific impact on the transcriptome. These findings demonstrate the value of ZFAs for functional annotation of repeats and illustrate how aberrant microsatellite activities might be regulated for potential therapeutic applications.","journal":"Cell Genomics","year":2022,"id":264048,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"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":98825,"name":"Gaylor Boulay","orcid":"0009-0001-7466-0760","position":1,"is_corresponding":false},{"id":921604,"name":"Lukuo Lee","orcid":"0000-0003-4215-2080","position":2,"is_corresponding":false},{"id":497360,"name":"Sowmya Iyer","orcid":"0000-0002-8058-7942","position":3,"is_corresponding":false},{"id":807908,"name":"Nicholas T. Perry","orcid":"0000-0002-1702-4178","position":4,"is_corresponding":false},{"id":921605,"name":"Hayley T. Schultz","orcid":"0000-0001-6115-057X","position":5,"is_corresponding":false},{"id":441304,"name":"Sara P. Garcia","orcid":"0000-0003-3312-6454","position":6,"is_corresponding":false},{"id":98827,"name":"Liliane C. Broye","orcid":null,"position":7,"is_corresponding":false},{"id":804334,"name":"Joy E. Horng","orcid":"0000-0001-7702-7381","position":8,"is_corresponding":false},{"id":849727,"name":"Shruthi Rengarajan","orcid":"0009-0009-0102-9597","position":9,"is_corresponding":false},{"id":921606,"name":"Beverly Naigles","orcid":"0000-0001-6115-5020","position":10,"is_corresponding":false},{"id":98824,"name":"Angela Volorio","orcid":null,"position":11,"is_corresponding":false},{"id":23565,"name":"Jeffry D. Sander","orcid":"0000-0002-4370-3182","position":12,"is_corresponding":false},{"id":292885,"name":"Jingyi Gong","orcid":"0000-0001-7848-1084","position":13,"is_corresponding":false},{"id":63704,"name":"Nicolò Riggi","orcid":"0000-0001-9160-1984","position":14,"is_corresponding":false},{"id":23566,"name":"J. Keith Joung","orcid":"0000-0001-5630-5645","position":15,"is_corresponding":false},{"id":5557,"name":"Miguel N. Rivera","orcid":"0000-0002-3636-2113","position":16,"is_corresponding":false},{"id":921603,"name":"Y. Esther Tak","orcid":"0000-0002-9588-1626","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:26:37.567338Z","pmid":"35967079","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":[]}