{"doi":"10.1126/sciadv.abf2229","title":"The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands","abstract":"CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.","journal":"Science Advances","year":2021,"id":164932,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":687577,"name":"Yuqiao Zhou","orcid":"0000-0002-9597-7513","position":1,"is_corresponding":false},{"id":687578,"name":"Yinghua Cao","orcid":"0000-0001-7804-1118","position":2,"is_corresponding":false},{"id":687579,"name":"Clara Simon","orcid":"0000-0002-0298-9858","position":3,"is_corresponding":false},{"id":687580,"name":"Hans‐Martin Pogoda","orcid":"0000-0003-3196-1720","position":4,"is_corresponding":false},{"id":687581,"name":"Junyi Jiang","orcid":"0000-0002-4080-069X","position":5,"is_corresponding":false},{"id":687582,"name":"Yanpeng Ren","orcid":"0000-0002-1899-0079","position":6,"is_corresponding":false},{"id":687583,"name":"Sabrina K. Phanor","orcid":"0000-0001-5540-9442","position":7,"is_corresponding":false},{"id":688497,"name":"Iris Rohner","orcid":null,"position":8,"is_corresponding":false},{"id":686187,"name":"Andrea Nist","orcid":"0000-0002-7524-6801","position":9,"is_corresponding":false},{"id":686188,"name":"Thorsten Stiewe","orcid":"0000-0003-0134-7826","position":10,"is_corresponding":false},{"id":413664,"name":"Matthias Hammerschmidt","orcid":"0000-0002-3709-8166","position":11,"is_corresponding":false},{"id":263374,"name":"Yang Shi","orcid":"0000-0001-9713-1709","position":12,"is_corresponding":false},{"id":557014,"name":"Martha L. Bulyk","orcid":"0000-0002-3456-4555","position":13,"is_corresponding":false},{"id":687584,"name":"Zhanxin Wang","orcid":"0000-0001-9956-9376","position":14,"is_corresponding":false},{"id":687585,"name":"Robert Liefke","orcid":"0000-0002-8549-637X","position":15,"is_corresponding":false},{"id":688496,"name":"Bastian Stielow","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:45:36.425208Z","pmid":"33980486","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":[]}