{"doi":"10.1101/gr.144840.112","title":"Interplay between chromatin state, regulator binding, and regulatory motifs in six human cell types","abstract":"The regions bound by sequence-specific transcription factors can be highly variable across different cell types despite the static nature of the underlying genome sequence. This has been partly attributed to changes in chromatin accessibility, but a systematic picture has been hindered by the lack of large-scale data sets. Here, we use 456 binding experiments for 119 regulators and 84 chromatin maps generated by the ENCODE in six human cell types, and relate those to a global map of regulatory motif instances for these factors. We find specific and robust chromatin state preferences for each regulator beyond the previously reported open-chromatin association, suggesting a much richer chromatin landscape beyond simple accessibility. The preferentially bound chromatin states of regulators were enriched for sequence motifs of regulators relative to all states, suggesting that these preferences are at least partly encoded by the genomic sequence. Relative to all regions bound by a regulator, however, regulatory motifs were surprisingly depleted in the regulator's preferentially bound states, suggesting additional non-sequence-specific binding beyond the level predicted by the regulatory motifs. Such permissive binding was largely restricted to open-chromatin regions showing histone modification marks characteristic of active enhancer and promoter regions, whereas open-chromatin regions lacking such marks did not show permissive binding. Lastly, the vast majority of cobinding of regulator pairs is predicted by the chromatin state preferences of individual regulators. Overall, our results suggest a joint role of sequence motifs and specific chromatin states beyond mere accessibility in mediating regulator binding dynamics across different cell types.","journal":"Genome Research","year":2013,"id":10916,"datarank":4.237203377236941,"base_score":4.634728988229636,"endowment":4.634728988229636,"self_citation_contribution":0.6952093482344455,"citation_network_contribution":3.5419940290024963,"self_endowment_contribution":0.6952093482344455,"citer_contribution":3.5419940290024963,"corpus_percentile":94.76289935793301,"corpus_rank":678,"citation_count":102,"citer_count":93,"citers_with_citation_signal":81,"citers_with_endowment":81,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.7044,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2013-04-17","fair_score":36.25,"fair_percentile":14.79028697571744,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":14693,"name":"Sharon L. 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Kardia","orcid":"0000-0002-9853-3379","position":1,"is_corresponding":false},{"id":859,"name":"Jason Ernst","orcid":"0000-0003-4026-7853","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"23595227","pmcid":"PMC3698507","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":52.5,"fair_a":42.5,"fair_i":25.0,"fair_r":25.0,"fair_zscore":-0.9287,"fair_rationale":{"fair_score":36.25,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":52.5,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper provides a DOI and references ENCODE data but lacks explicit machine-readable metadata or structured data citation."}]},"A":{"name":"Accessible","score":42.5,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper mentions a URL for motif data but does not provide a clear, comprehensive protocol for accessing all data and code used."}]},"I":{"name":"Interoperable","score":25.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.5,"signal":null,"rationale":"The paper uses standard genomic coordinates, cell line identifiers, and chromatin state definitions, but does not specify file formats or formal vocabularies for its own outputs."}]},"R":{"name":"Reusable","score":25.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.333,"signal":null,"rationale":"The paper has a Creative Commons license and supplemental material, but lacks a data availability statement and does not provide code or processed data in a repository."}]}},"suggestions":["Add a data availability statement with persistent identifiers (e.g., DOI) for all processed data and code.","Deposit analysis code in a public repository (e.g., GitHub) and link it in the paper.","Include machine-readable metadata (e.g., schema.org markup) in the article's HTML version.","Specify file formats (e.g., BED, bigWig) used for data to improve interoperability.","Provide accession numbers for all ENCODE datasets used to facilitate direct access."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v2","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v2","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-06-18T00:40:09.184472Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}