{"doi":"10.1101/2023.05.22.541769","title":"Dynamic enhancer interactome promotes senescence and aging","abstract":"Gene expression programs are regulated by enhancers which act in a context-specific manner, and can reside at great distances from their target genes. Extensive three-dimensional (3D) genome reorganization occurs in senescence, but how enhancer interactomes are reconfigured during this process is just beginning to be understood. Here we generated high-resolution contact maps of active enhancers and their target genes, assessed chromatin accessibility, and established one-dimensional maps of various histone modifications and transcription factors to comprehensively understand the regulation of enhancer configuration during senescence. Hyper-connected enhancer communities/cliques formed around genes that are highly expressed and within essential gene pathways in each cell state. In addition, motif analysis indicates the involvement of specific transcription factors in hyper-connected regulatory elements in each condition; importantly, MafK, a bZIP family transcription factor, was upregulated in senescence, and reduced expression of MafK ameliorated the senescence phenotypes. Because the accumulation of senescent cells is a key feature of aging, we further investigated enhancer connectomes in the liver of young and aged mice. Hyper-connected enhancer communities were identified during aging, which regulate essential genes that maintain cell differentiation and homeostasis. These findings reveal that hyper-connected enhancer communities correlate with high gene expression in senescence and aging and provide potential hotspots for therapeutic intervention in aging and age-associated diseases.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391820,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"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":1164995,"name":"Gregory Donahue","orcid":null,"position":1,"is_corresponding":false},{"id":1164536,"name":"Chen Zhang","orcid":"0000-0001-8592-3936","position":2,"is_corresponding":false},{"id":847686,"name":"Aaron Havas","orcid":"0000-0003-4291-8015","position":3,"is_corresponding":false},{"id":549953,"name":"Xue Lei","orcid":"0000-0001-9647-3782","position":4,"is_corresponding":false},{"id":227831,"name":"Caiyue Xu","orcid":"0000-0003-4056-5586","position":5,"is_corresponding":false},{"id":326064,"name":"Wenliang Wang","orcid":"0000-0003-0575-8139","position":6,"is_corresponding":false},{"id":250527,"name":"Golnaz Vahedi","orcid":"0000-0002-2249-8247","position":7,"is_corresponding":false},{"id":227838,"name":"Peter D. Adams","orcid":"0000-0002-0684-1770","position":8,"is_corresponding":false},{"id":227842,"name":"Shelley L. Berger","orcid":"0000-0001-5398-4400","position":9,"is_corresponding":false},{"id":227832,"name":"Lu Wang","orcid":"0000-0002-8896-0115","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:18:47.408273Z","pmid":"37292952","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":[]}