{"doi":"10.1101/2023.11.20.567954","title":"Cellular zinc status alters chromatin accessibility and binding of transcription factor p53 to genomic sites","abstract":"Abstract Zinc (Zn 2+ ) is an essential metal required by approximately 2500 proteins. Nearly half of these proteins act on DNA, including > 850 human transcription factors, polymerases, DNA damage response factors, and proteins involved in chromatin architecture. How these proteins acquire their essential Zn 2+ cofactor and whether they are sensitive to changes in the labile Zn 2+ pool in cells remain open questions. Here, we examine how changes in the labile Zn 2+ pool affect chromatin accessibility and transcription factor binding to DNA. We observed both increases and decreases in accessibility in different chromatin regions via ATAC-seq upon treating MCF10A cells with elevated Zn 2+ or the Zn 2+ -specific chelator tris(2-pyridylmethyl)amine (TPA). Transcription factor enrichment analysis was used to correlate changes in chromatin accessibility with transcription factor motifs, revealing 477 transcription factor motifs that were differentially enriched upon Zn 2+ perturbation. 186 of these transcription factor motifs were enriched in Zn 2+ and depleted in TPA, and the majority correspond to Zn 2+ finger transcription factors. We selected TP53 as a candidate to examine how changes in motif enrichment correlate with changes in transcription factor occupancy by ChIP-qPCR. Using publicly available ChIP-seq and nascent transcription datasets, we narrowed the 50,000+ ATAC-seq peaks to 2164 TP53 targets and subsequently selected 6 high-probability TP53 binding sites for testing. ChIP-qPCR revealed that for 5 of the 6 targets, TP53 binding correlates with the local accessibility determined by ATAC-seq. These results demonstrate that changes in labile zinc directly alter chromatin accessibility and transcription factor binding to DNA.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":401668,"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":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":926053,"name":"Daniel Ocampo","orcid":"0000-0002-8412-2835","position":1,"is_corresponding":false},{"id":579391,"name":"Lynn Sanford","orcid":"0000-0002-1255-556X","position":2,"is_corresponding":false},{"id":106509,"name":"Taylor Jones","orcid":"0000-0002-8591-2847","position":3,"is_corresponding":false},{"id":625949,"name":"Mary A. Allen","orcid":"0000-0001-7490-0165","position":4,"is_corresponding":false},{"id":28295,"name":"Robin D. Dowell","orcid":"0000-0001-7665-9985","position":5,"is_corresponding":false},{"id":266286,"name":"Amy E. Palmer","orcid":"0000-0002-5794-5983","position":6,"is_corresponding":false},{"id":299144,"name":"Leah J. Damon","orcid":"0000-0002-0863-0328","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T01:20:12.316631Z","pmid":"38045276","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":[]}