{"doi":"10.1101/2023.02.15.528714","title":"Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging","abstract":"DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395824,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"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":1027710,"name":"Na Yang","orcid":"0000-0002-6956-6630","position":1,"is_corresponding":false},{"id":575586,"name":"Yan Sun","orcid":"0000-0002-5747-3306","position":2,"is_corresponding":false},{"id":1171332,"name":"Marshall S. Dawkins","orcid":null,"position":3,"is_corresponding":false},{"id":252579,"name":"Rachel Munk","orcid":null,"position":4,"is_corresponding":false},{"id":1155320,"name":"Cédric Belair","orcid":"0000-0003-4007-2060","position":5,"is_corresponding":false},{"id":1170976,"name":"Showkat Ahmad Dar","orcid":"0000-0002-7858-4320","position":6,"is_corresponding":false},{"id":254790,"name":"Carlos Anerillas","orcid":"0000-0003-4424-7913","position":7,"is_corresponding":false},{"id":424212,"name":"Lin Wang","orcid":"0000-0002-2148-1929","position":8,"is_corresponding":false},{"id":425306,"name":"Changyou Shi","orcid":null,"position":9,"is_corresponding":false},{"id":323574,"name":"Christopher Dunn","orcid":"0000-0001-7899-0110","position":10,"is_corresponding":false},{"id":115050,"name":"Michel Bernier","orcid":"0000-0002-5948-368X","position":11,"is_corresponding":false},{"id":291047,"name":"Nathan L. Price","orcid":"0000-0002-2821-9608","position":12,"is_corresponding":false},{"id":949322,"name":"Julie S. Kim","orcid":"0009-0004-2940-4241","position":13,"is_corresponding":false},{"id":467285,"name":"Chang‐Yi Cui","orcid":"0000-0002-9856-9427","position":14,"is_corresponding":false},{"id":210682,"name":"JINSHUI FAN","orcid":null,"position":15,"is_corresponding":false},{"id":564468,"name":"Moitrayee Bhattacharyya","orcid":"0000-0002-2168-1541","position":16,"is_corresponding":false},{"id":275722,"name":"Supriyo De","orcid":"0000-0002-2075-7655","position":17,"is_corresponding":false},{"id":424975,"name":"Manolis Maragkakis","orcid":"0000-0002-3158-1763","position":18,"is_corresponding":false},{"id":1171333,"name":"Rafael deCabo","orcid":null,"position":19,"is_corresponding":false},{"id":247704,"name":"Simone Sidoli","orcid":"0000-0001-9073-6641","position":20,"is_corresponding":false},{"id":275721,"name":"Payel Sen","orcid":"0000-0003-2809-0901","position":21,"is_corresponding":false},{"id":685306,"name":"James R. Occean","orcid":"0000-0002-6823-6381","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:19:22.857556Z","pmid":"36824863","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":[]}