{"doi":"10.1371/journal.pcbi.0030099","title":"Frequent Gain and Loss of Functional Transcription Factor Binding Sites","abstract":null,"journal":"PLoS Computational Biology","year":2007,"id":602094,"datarank":0.7631394502848576,"base_score":5.087596335232384,"endowment":5.087596335232384,"self_citation_contribution":0.7631394502848576,"citation_network_contribution":0.0,"self_endowment_contribution":0.7631394502848576,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":161,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1544069,"name":"Justin C Fay","orcid":null,"position":1,"is_corresponding":false},{"id":1544068,"name":"Scott W Doniger","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Frequent Gain and Loss of Functional Transcription Factor Binding Sites","abstract":"Cis-regulatory sequences are not always conserved across species. Divergence within cis-regulatory sequences may result from the evolution of species-specific patterns of gene expression or the flexible nature of the cis-regulatory code. The identification of functional divergence in cis-regulatory sequences is therefore important for both understanding the role of gene regulation in evolution and annotating regulatory elements. We have developed an evolutionary model to detect the loss of constraint on individual transcription factor binding sites (TFBSs). We find that a significant fraction of functionally constrained binding sites have been lost in a lineage-specific manner among three closely related yeast species. Binding site loss has previously been explained by turnover, where the concurrent gain and loss of a binding site maintains gene regulation. We estimate that nearly half of all loss events cannot be explained by binding site turnover. Recreating the mutations that led to binding site loss confirms that these sequence changes affect gene expression in some cases. We also estimate that there is a high rate of binding site gain, as more than half of experimentally identified S. cerevisiae binding sites are not conserved across species. The frequent gain and loss of TFBSs implies that cis-regulatory sequences are labile and, in the absence of turnover, may contribute to species-specific patterns of gene expression.","is_dataset_classified":null,"base_score":5.087596335232384,"endowment":5.087596335232384,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17530920","pmcid":"PMC1876492","openalex_id":"https://openalex.org/W2030816054","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM080669","title":null},{"funder_name":"National Science Foundation","grant_id":"0202737","title":"Graduate Research Fellowship"}],"total_grants":2,"fwci":6.4123,"citation_percentile":0.97595021,"influential_citations":0,"citation_trend":[{"year":2012,"count":13},{"year":2013,"count":9},{"year":2014,"count":15},{"year":2015,"count":8},{"year":2016,"count":12},{"year":2017,"count":5},{"year":2018,"count":3},{"year":2019,"count":6},{"year":2020,"count":3},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2023,"count":1},{"year":2024,"count":4},{"year":2025,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.0030099&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.0030099&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pcbi.0030099","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pcbi.0030099","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17530920","host_type":"repository"},{"url":"https://digitalcommons.wustl.edu/open_access_pubs/459","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.279.9834","host_type":""},{"url":"https://doaj.org/article/a379c382f65140adabb6397a4e90e556","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Frequent_Gain_and_Loss_of_Functional_Transcription_Factor_Binding_Sites/152068","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1876492","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC1876492","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC1876492?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1371/journal.pcbi.0030099.eor","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pcbi.0030099","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pcbi.0030099","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pcbi.0030099","host_type":""}],"fields_of_study":["Fungal and yeast genetics research","Genomics and Chromatin Dynamics","Bioinformatics and Genomic Networks","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Base Sequence","Binding Sites","Gene Frequency","Molecular Sequence Data","Protein Binding","Regulatory Sequences, Nucleic Acid","Saccharomyces cerevisiae","Transcription Factors","Genetic Variation","Sequence Analysis, DNA","Evolution, Molecular","Saccharomyces cerevisiae Proteins"],"keywords":["DNA binding site","Biology","Binding site","Transcription factor","Gene","Regulatory sequence","Genetics","Functional divergence","Regulation of gene expression","Lineage (genetic)","Conserved sequence","Gene expression","Evolutionary biology","Computational biology","Promoter","Gene family","Peptide sequence","Binding Sites","Saccharomyces cerevisiae Proteins","Base Sequence","QH301-705.5","Molecular Sequence Data","Genetic Variation","Saccharomyces cerevisiae","Sequence Analysis, DNA","Regulatory Sequences, Nucleic Acid","Evolution, Molecular","Gene Frequency","Medicine and Health Sciences","Biology (General)","Research Article","Protein Binding","Transcription Factors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T18:16:54.227266Z","pmid":null,"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":[]}