{"doi":"10.7554/elife.59404","title":"Massively multiplex single-molecule oligonucleosome footprinting","abstract":"Our understanding of the beads-on-a-string arrangement of nucleosomes has been built largely on high-resolution sequence-agnostic imaging methods and sequence-resolved bulk biochemical techniques. To bridge the divide between these approaches, we present the single-molecule adenine methylated oligonucleosome sequencing assay (SAMOSA). SAMOSA is a high-throughput single-molecule sequencing method that combines adenine methyltransferase footprinting and single-molecule real-time DNA sequencing to natively and nondestructively measure nucleosome positions on individual chromatin fibres. SAMOSA data allows unbiased classification of single-molecular 'states' of nucleosome occupancy on individual chromatin fibres. We leverage this to estimate nucleosome regularity and spacing on single chromatin fibres genome-wide, at predicted transcription factor binding motifs, and across human epigenomic domains. Our analyses suggest that chromatin is comprised of both regular and irregular single-molecular oligonucleosome patterns that differ subtly in their relative abundance across epigenomic domains. This irregularity is particularly striking in constitutive heterochromatin, which has typically been viewed as a conformationally static entity. Our proof-of-concept study provides a powerful new methodology for studying nucleosome organization at a previously intractable resolution and offers up new avenues for modeling and visualizing higher order chromatin structure.","journal":"eLife","year":2020,"id":52700,"datarank":3.3528706090477196,"base_score":4.867534450455582,"endowment":4.867534450455582,"self_citation_contribution":0.7301301675683375,"citation_network_contribution":2.6227404414793822,"self_endowment_contribution":0.7301301675683375,"citer_contribution":2.6227404414793822,"corpus_percentile":null,"corpus_rank":null,"citation_count":129,"citer_count":100,"citers_with_citation_signal":86,"citers_with_endowment":86,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE162410","SRP252718"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":267295,"name":"Colin P McNally","orcid":"0000-0002-2169-5302","position":1,"is_corresponding":false},{"id":267296,"name":"Laura J Hsieh","orcid":"0000-0002-7615-6226","position":2,"is_corresponding":false},{"id":267297,"name":"Sivakanthan Kasinathan","orcid":"0000-0003-2218-6371","position":3,"is_corresponding":false},{"id":267298,"name":"Aidan Keith","orcid":"0000-0002-2675-5538","position":4,"is_corresponding":false},{"id":267299,"name":"Laurel S. Estes","orcid":"0000-0002-8876-1482","position":5,"is_corresponding":false},{"id":52777,"name":"Mehran Karimzadeh","orcid":"0000-0002-7324-6074","position":6,"is_corresponding":false},{"id":56431,"name":"Jason G. Underwood","orcid":null,"position":7,"is_corresponding":false},{"id":43301,"name":"Hani Goodarzi","orcid":"0000-0002-9648-8949","position":8,"is_corresponding":false},{"id":6711,"name":"Geeta J. Narlikar","orcid":"0000-0002-1920-0147","position":9,"is_corresponding":false},{"id":29908,"name":"Vijay Ramani","orcid":"0000-0003-3345-5960","position":10,"is_corresponding":false},{"id":98612,"name":"Nour J. Abdulhay","orcid":"0000-0002-2794-3776","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T20:43:25.742124Z","pmid":"33263279","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":[]}