{"doi":"10.1128/mbio.00523-16","title":"Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis Shows that WhiB Is a Transcription Factor That Cocontrols Its Regulon with WhiA To Initiate Developmental Cell Division in\n                    <i>Streptomyces</i>","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>\n                    WhiB is the founding member of a family of proteins (the\n                    <jats:underline>W</jats:underline>\n                    hi\n                    <jats:underline>B</jats:underline>\n                    -\n                    <jats:underline>l</jats:underline>\n                    ike [Wbl] family) that carry a [4Fe-4S] iron-sulfur cluster and play key roles in diverse aspects of the biology of actinomycetes, including pathogenesis, antibiotic resistance, and the control of development. In\n                    <jats:italic>Streptomyces</jats:italic>\n                    , WhiB is essential for the process of developmentally controlled cell division that leads to sporulation. The biochemical function of Wbl proteins has been controversial; here, we set out to determine unambiguously if WhiB functions as a transcription factor using chromatin immunoprecipitation sequencing (ChIP-seq) in\n                    <jats:named-content content-type=\"genus-species\">Streptomyces venezuelae</jats:named-content>\n                    . In the first demonstration of\n                    <jats:italic>in vivo</jats:italic>\n                    genome-wide Wbl binding, we showed that WhiB regulates the expression of key genes required for sporulation by binding upstream of ~240 transcription units. Strikingly, the WhiB regulon is identical to the previously characterized WhiA regulon, providing an explanation for the identical phenotypes of\n                    <jats:italic>whiA</jats:italic>\n                    and\n                    <jats:italic>whiB</jats:italic>\n                    mutants. Using ChIP-seq, we demonstrated that\n                    <jats:italic>in vivo</jats:italic>\n                    DNA binding by WhiA depends on WhiB and vice versa, showing that WhiA and WhiB function cooperatively to control expression of a common set of WhiAB target genes. Finally, we show that mutation of the cysteine residues that coordinate the [4Fe-4S] cluster in WhiB prevents DNA binding by both WhiB and WhiA\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE</jats:bold>\n                    Despite the central importance of\n                    <jats:underline>W</jats:underline>\n                    hi\n                    <jats:underline>B</jats:underline>\n                    -\n                    <jats:underline>l</jats:underline>\n                    ike (Wbl) proteins in actinomycete biology, a conclusive demonstration of their biochemical function has been elusive, and they have been difficult to study, particularly\n                    <jats:italic>in vitro</jats:italic>\n                    , largely because they carry an oxygen-sensitive [4Fe-4S] cluster. Here we used genome-wide ChIP-seq to investigate the function of\n                    <jats:italic>Streptomyces</jats:italic>\n                    WhiB, the founding member of the Wbl family. The advantage of this approach is that the oxygen sensitivity of the [4Fe-4S] cluster becomes irrelevant once the protein has been cross-linked to DNA\n                    <jats:italic>in vivo</jats:italic>\n                    . Our data provide the most compelling\n                    <jats:italic>in vivo</jats:italic>\n                    evidence to date that WhiB, and, by extension, probably all Wbl proteins, function as transcription factors. Further, we show that WhiB does not act independently but rather coregulates its regulon of sporulation genes with a partner transcription factor, WhiA.\n                  </jats:p>","journal":"mBio","year":2016,"id":638865,"datarank":0.6892679775201885,"base_score":4.59511985013459,"endowment":4.59511985013459,"self_citation_contribution":0.6892679775201885,"citation_network_contribution":0.0,"self_endowment_contribution":0.6892679775201885,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":98,"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":571454,"name":"Govind Chandra","orcid":"0000-0002-7882-6676","position":1,"is_corresponding":false},{"id":1659609,"name":"Maureen J. Bibb","orcid":null,"position":2,"is_corresponding":false},{"id":1659613,"name":"Kim C. Findlay","orcid":null,"position":3,"is_corresponding":false},{"id":770568,"name":"Mark J. Buttner","orcid":"0000-0002-3505-2981","position":4,"is_corresponding":false},{"id":571452,"name":"Matthew J. Bush","orcid":"0000-0001-8216-0152","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis Shows that WhiB Is a Transcription Factor That Cocontrols Its Regulon with WhiA To Initiate Developmental Cell Division in\n                    <i>Streptomyces</i>","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>\n                    WhiB is the founding member of a family of proteins (the\n                    <jats:underline>W</jats:underline>\n                    hi\n                    <jats:underline>B</jats:underline>\n                    -\n                    <jats:underline>l</jats:underline>\n                    ike [Wbl] family) that carry a [4Fe-4S] iron-sulfur cluster and play key roles in diverse aspects of the biology of actinomycetes, including pathogenesis, antibiotic resistance, and the control of development. In\n                    <jats:italic>Streptomyces</jats:italic>\n                    , WhiB is essential for the process of developmentally controlled cell division that leads to sporulation. The biochemical function of Wbl proteins has been controversial; here, we set out to determine unambiguously if WhiB functions as a transcription factor using chromatin immunoprecipitation sequencing (ChIP-seq) in\n                    <jats:named-content content-type=\"genus-species\">Streptomyces venezuelae</jats:named-content>\n                    . In the first demonstration of\n                    <jats:italic>in vivo</jats:italic>\n                    genome-wide Wbl binding, we showed that WhiB regulates the expression of key genes required for sporulation by binding upstream of ~240 transcription units. Strikingly, the WhiB regulon is identical to the previously characterized WhiA regulon, providing an explanation for the identical phenotypes of\n                    <jats:italic>whiA</jats:italic>\n                    and\n                    <jats:italic>whiB</jats:italic>\n                    mutants. Using ChIP-seq, we demonstrated that\n                    <jats:italic>in vivo</jats:italic>\n                    DNA binding by WhiA depends on WhiB and vice versa, showing that WhiA and WhiB function cooperatively to control expression of a common set of WhiAB target genes. Finally, we show that mutation of the cysteine residues that coordinate the [4Fe-4S] cluster in WhiB prevents DNA binding by both WhiB and WhiA\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE</jats:bold>\n                    Despite the central importance of\n                    <jats:underline>W</jats:underline>\n                    hi\n                    <jats:underline>B</jats:underline>\n                    -\n                    <jats:underline>l</jats:underline>\n                    ike (Wbl) proteins in actinomycete biology, a conclusive demonstration of their biochemical function has been elusive, and they have been difficult to study, particularly\n                    <jats:italic>in vitro</jats:italic>\n                    , largely because they carry an oxygen-sensitive [4Fe-4S] cluster. Here we used genome-wide ChIP-seq to investigate the function of\n                    <jats:italic>Streptomyces</jats:italic>\n                    WhiB, the founding member of the Wbl family. The advantage of this approach is that the oxygen sensitivity of the [4Fe-4S] cluster becomes irrelevant once the protein has been cross-linked to DNA\n                    <jats:italic>in vivo</jats:italic>\n                    . Our data provide the most compelling\n                    <jats:italic>in vivo</jats:italic>\n                    evidence to date that WhiB, and, by extension, probably all Wbl proteins, function as transcription factors. Further, we show that WhiB does not act independently but rather coregulates its regulon of sporulation genes with a partner transcription factor, WhiA.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.59511985013459,"endowment":4.59511985013459,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27094333","pmcid":"PMC4850268","openalex_id":"https://openalex.org/W2336421362","authors":[],"funders":[{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/I00873X/1","title":"Molecular mechanism of environmental stress sensing by bacterial Zinc-containing Anti-Sigma factors"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/L019825/1","title":null},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BBS/E/J/00000015","title":null},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/H006125/1","title":"Characterisation of BldC a novel transcription factor required for development and antibiotic production in Streptomyces"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/J004561/1","title":null}],"total_grants":5,"fwci":10.3822,"citation_percentile":0.98523292,"influential_citations":0,"citation_trend":[{"year":2016,"count":5},{"year":2017,"count":17},{"year":2018,"count":7},{"year":2019,"count":6},{"year":2020,"count":17},{"year":2021,"count":17},{"year":2022,"count":9},{"year":2023,"count":8},{"year":2024,"count":1},{"year":2025,"count":5},{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://mbio.asm.org/content/mbio/7/2/e00523-16.full.pdf","host_type":"journal"},{"url":"https://mbio.asm.org/content/mbio/7/2/e00523-16.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/mBio.00523-16","host_type":"publisher"},{"url":"https://doi.org/10.1128/mbio.00523-16","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27094333","host_type":"repository"},{"url":"https://doaj.org/article/2eb32ce2b9e041b188a851190109dbab","host_type":"repository"},{"url":"https://doaj.org/article/3807c87671834867950e3a905495d361","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4850268","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4850268","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4850268?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1128/mBio.00523-16","host_type":""},{"url":"https://dx.doi.org/10.1128/mbio.00523-16","host_type":""}],"fields_of_study":["Microbial Natural Products and Biosynthesis","Metalloenzymes and iron-sulfur proteins","Bacterial Genetics and Biotechnology","0301 basic medicine","03 medical and health sciences","Bacterial Proteins","Cell Division","Chromatin Immunoprecipitation","Gene Expression Regulation, Bacterial","Gene Expression Regulation, Developmental","Genome, Bacterial","Regulon","Streptomyces","Transcription Factors"],"mesh_terms":["Bacterial Proteins","Cell Division","Streptomyces","Transcription Factors","Gene Expression Regulation, Bacterial","Genome, Bacterial","Regulon","Gene Expression Regulation, Developmental","Chromatin Immunoprecipitation"],"keywords":["Regulon","Chromatin immunoprecipitation","Biology","Transcription factor","Genetics","Streptomyces","Transcription (linguistics)","Gene","Chromatin","DNA-binding protein","DNA","Computational biology","Promoter","Gene expression","Bacteria","Gene Expression Regulation, Developmental","Gene Expression Regulation, Bacterial","Microbiology","QR1-502","Bacterial Proteins","Cell Division","Genome, Bacterial","Research Article","Transcription Factors"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T21:45:21.650191Z","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":[]}