{"doi":"10.1083/jcb.145.7.1341","title":"Large-Scale Chromatin Unfolding and Remodeling Induced by VP16 Acidic Activation Domain","abstract":"<jats:p>Analysis of the relationship between transcriptional activators and chromatin organization has focused largely on lower levels of chromatin structure. Here we describe striking remodeling of large-scale chromatin structure induced by a strong transcriptional activator. A VP16-lac repressor fusion protein targeted the VP16 acidic activation domain to chromosome regions containing lac operator repeats. Targeting was accompanied by increased transcription, localized histone hyperacetylation, and recruitment of at least three different histone acetyltransferases. Observed effects on large-scale chromatin structure included unfolding of a 90-Mbp heterochromatic chromosome arm into an extended 25–40-μm chromonema fiber, remodeling of this fiber into a novel subnuclear domain, and propagation of large-scale chromatin unfolding over hundreds of kilobase pairs. These changes in large-scale chromatin structure occurred even with inhibition of ongoing transcription by α-amanitin. Our results suggest a functional link between recruitment of the transcriptional machinery and changes in large-scale chromatin structure. Based on the observed long-range propagation of changes in large-scale chromatin structure, we suggest a possible rationale for the observed clustering of housekeeping genes within Mbp-sized chromosome bands.</jats:p>","journal":"The Journal of Cell Biology","year":1999,"id":15279,"datarank":13.586770868443377,"base_score":5.860786223465865,"endowment":5.860786223465865,"self_citation_contribution":0.87911793351988,"citation_network_contribution":12.707652934923496,"self_endowment_contribution":0.87911793351988,"citer_contribution":12.707652934923496,"corpus_percentile":null,"corpus_rank":null,"citation_count":350,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":117235,"name":"Gail Sudlow","orcid":null,"position":1,"is_corresponding":false},{"id":117236,"name":"Andrew S. Belmont","orcid":null,"position":2,"is_corresponding":false},{"id":117234,"name":"Tudorita Tumbar","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.860786223465865,"endowment":5.860786223465865,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10385516","pmcid":"PMC2133171","openalex_id":"https://openalex.org/W2138165389","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01-GM42516","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM042516","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM042516-16","title":"Large-scale chromatin structure and dynamics"}],"total_grants":3,"fwci":6.02,"citation_percentile":0.9709616,"influential_citations":26,"citation_trend":[{"year":2012,"count":13},{"year":2013,"count":17},{"year":2014,"count":6},{"year":2015,"count":12},{"year":2016,"count":8},{"year":2017,"count":5},{"year":2018,"count":6},{"year":2019,"count":9},{"year":2020,"count":5},{"year":2021,"count":7},{"year":2022,"count":5},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://rupress.org/jcb/article-pdf/145/7/1341/1286333/9904063.pdf","host_type":"journal"},{"url":"https://rupress.org/jcb/article-pdf/145/7/1341/1286333/9904063.pdf","host_type":"BRONZE"},{"url":"https://rupress.org/jcb/article-pdf/145/7/1341/1286333/9904063.pdf","host_type":"publisher"},{"url":"https://rupress.org/jcb/article-pdf/145/7/1341/1849307/9904063.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1083/jcb.145.7.1341","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10385516","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.274.1183","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2133171","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2133171","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2133171?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.1083/jcb.145.7.1341","host_type":""}],"fields_of_study":["Genomics and Chromatin Dynamics","Ubiquitin and proteasome pathways","RNA Research and Splicing","Biology","Medicine","0301 basic medicine","03 medical and health sciences","Acetylation","Acetyltransferases","Animals","Bacterial Proteins","CHO Cells","Chromatin","Cricetinae","Escherichia coli Proteins","Genome","Herpes Simplex Virus Protein Vmw65","Heterochromatin","Histone Acetyltransferases","Histones","Lac Repressors","Molecular Conformation","Operator Regions, Genetic","Recombinant Fusion Proteins","Repressor Proteins","Saccharomyces cerevisiae Proteins","Time Factors","Transcription, Genetic","Transcriptional Activation","Transfection"],"mesh_terms":["Acetylation","Acetyltransferases","Animals","Bacterial Proteins","Chromatin","Cricetinae","Heterochromatin","Histones","Molecular Conformation","Operator Regions, Genetic","Recombinant Fusion Proteins","Repressor Proteins","Time Factors","Transcription, Genetic","Transfection","Transcriptional Activation","CHO Cells","Genome","Herpes Simplex Virus Protein Vmw65","Saccharomyces cerevisiae Proteins","Escherichia coli Proteins","Histone Acetyltransferases","Lac Repressors"],"keywords":["Chromatin","Chromatin remodeling","Histone-modifying enzymes","ChIA-PET","Biology","Scaffold/matrix attachment region","Histone","Cell biology","Bivalent chromatin","Heterochromatin","Genetics","Gene","Genome","Operator Regions, Genetic","Saccharomyces cerevisiae Proteins","Time Factors","Escherichia coli Proteins","Recombinant Fusion Proteins","Molecular Conformation","Acetylation","Herpes Simplex Virus Protein Vmw65","CHO Cells","Histones","Repressor Proteins","Bacterial Proteins","Acetyltransferases","Cricetinae","Lac Repressors","Animals","Histone Acetyltransferases"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T17:07:10.268310Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}