{"doi":"10.15252/embr.202356902","title":"Molecular mechanisms of TWIST1‐regulated transcription in EMT and cancer metastasis","abstract":"TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis. TWIST1 interacts with both the NuRD complex and the NuA4/TIP60 complex (TIP60-Com) via its N-terminus. Non-acetylated TWIST1-K73/76 selectively interacts with and recruits NuRD to repress epithelial target gene transcription. Diacetylated TWIST1-acK73/76 binds BRD8, a component of TIP60-Com that also binds histone H4-acK5/8, to recruit TIP60-Com to activate mesenchymal target genes and MYC. Knockdown of BRD8 abolishes TWIST1 and TIP60-Com interaction and TIP60-Com recruitment to TWIST1-activated genes, resulting in decreasing TWIST1-activated target gene expression and cancer metastasis. Both TWIST1/NuRD and TWIST1/TIP60-Com complexes are required for TWIST1 to promote EMT, proliferation, and metastasis at full capacity. Therefore, the diacetylation status of TWIST1-K73/76 dictates whether TWIST1 interacts either with NuRD to repress epithelial genes, or with TIP60-Com to activate mesenchymal genes and MYC. Since BRD8 is essential for TWIST1-acK73/76 and TIP60-Com interaction, targeting BRD8 could be a means to inhibit TWIST1-activated gene expression.","journal":"EMBO Reports","year":2023,"id":320849,"datarank":1.087646591826285,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"self_citation_contribution":0.5806801516361837,"citation_network_contribution":0.5069664401901013,"self_endowment_contribution":0.5806801516361837,"citer_contribution":0.5069664401901013,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":43,"citers_with_citation_signal":28,"citers_with_endowment":28,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE189828"]},"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":1032166,"name":"Tao He","orcid":"0000-0002-1533-0761","position":1,"is_corresponding":false},{"id":1032167,"name":"Zhangwei Tong","orcid":"0009-0003-3483-6826","position":2,"is_corresponding":false},{"id":524949,"name":"Lan Liao","orcid":"0000-0002-1004-4344","position":3,"is_corresponding":false},{"id":2210,"name":"Shixia Huang","orcid":"0000-0003-2878-4129","position":4,"is_corresponding":false},{"id":63739,"name":"Walid D. Fakhouri","orcid":"0000-0002-2199-3828","position":5,"is_corresponding":false},{"id":2211,"name":"Dean P. Edwards","orcid":null,"position":6,"is_corresponding":false},{"id":460773,"name":"Jianming Xu","orcid":"0000-0002-8208-9162","position":7,"is_corresponding":false},{"id":638478,"name":"Xiaobin Yu","orcid":"0000-0002-9727-351X","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:07:27.434133Z","pmid":"37680145","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":[]}