{"doi":"10.1093/nar/gkac760","title":"The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and REST-binding sequences to maintain nephron progenitor identity","abstract":"Eya1 is critical for establishing and maintaining nephron progenitor cells (NPCs). It belongs to a family of proteins called phosphatase-transcriptional activators but without intrinsic DNA-binding activity. However, the spectrum of the Eya1-centered networks is underexplored. Here, we combined transcriptomic, genomic and proteomic approaches to characterize gene regulation by Eya1 in the NPCs. We identified Eya1 target genes, associated cis-regulatory elements and partner proteins. Eya1 preferentially occupies promoter sequences and interacts with general transcription factors (TFs), RNA polymerases, different types of TFs, chromatin-remodeling factors with ATPase or helicase activity, and DNA replication/repair proteins. Intriguingly, we identified REST-binding motifs in 76% of Eya1-occupied sites without H3K27ac-deposition, which were present in many Eya1 target genes upregulated in Eya1-deficient NPCs. Eya1 copurified REST-interacting chromatin-remodeling factors, histone deacetylase/lysine demethylase, and corepressors. Coimmunoprecipitation validated physical interaction between Eya1 and Rest/Hdac1/Cdyl/Hltf in the kidneys. Collectively, our results suggest that through interactions with chromatin-remodeling factors and specialized DNA-binding proteins, Eya1 may modify chromatin structure to facilitate the assembly of regulatory complexes that regulate transcription positively or negatively. These findings provide a mechanistic basis for how Eya1 exerts its activity by forming unique multiprotein complexes in various biological processes to maintain the cellular state of NPCs.","journal":"Nucleic Acids Research","year":2022,"id":262406,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":232150,"name":"Chunming Cheng","orcid":"0000-0001-9036-1683","position":1,"is_corresponding":false},{"id":328293,"name":"Jin Xu","orcid":"0000-0002-6287-5633","position":2,"is_corresponding":false},{"id":328290,"name":"Ting Zhang","orcid":"0000-0001-9231-1604","position":3,"is_corresponding":false},{"id":492898,"name":"Bengü Tokat","orcid":null,"position":4,"is_corresponding":false},{"id":691940,"name":"Georgia Dolios","orcid":"0009-0008-2746-6317","position":5,"is_corresponding":false},{"id":328291,"name":"Aarthi Ramakrishnan","orcid":"0000-0002-6329-6502","position":6,"is_corresponding":false},{"id":328296,"name":"Li Shen","orcid":"0000-0002-5190-2851","position":7,"is_corresponding":false},{"id":770460,"name":"Rong Wang","orcid":"0000-0002-9947-4307","position":8,"is_corresponding":false},{"id":328297,"name":"Pin‐Xian Xu","orcid":"0000-0002-8957-6780","position":9,"is_corresponding":false},{"id":328289,"name":"Jun Li","orcid":"0000-0002-1746-6793","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T00:26:20.717229Z","pmid":"36130284","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":[]}