{"doi":"10.1128/spectrum.01004-25","title":"Deciphering the role of\n                    <i>Th</i>\n                    HSF1 in the differential expression regulation of laccase isozymes in the white-rot fungus\n                    <i>Trametes hirsuta</i>","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title/>\n                    <jats:p>\n                      White-rot fungi exhibit responses to Cu\n                      <jats:sup>2+</jats:sup>\n                      , leading to a substantial increase in the production of certain laccase isozymes for industry utilization. Currently, studies on the differential expression mechanism of the laccase isozymes in white-rot fungi are limited. Three laccase isozymes, LacA, LacB, and LacF, were significantly induced in\n                      <jats:italic toggle=\"yes\">Trametes hirsuta</jats:italic>\n                      AH28-2 when exposed to Cu\n                      <jats:sup>2+</jats:sup>\n                      , accompanied by a slight enhancement in the isozyme LacC level. Here, based on transcriptomics and proteomics, a nuclear-localized heat shock transcription factor,\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1, was mined and exhibited as a copper-responsive protein involved in the differential regulation of laccase isozyme expression. A changed colony morphology and curved hyphal morphology were observed in three\n                      <jats:italic toggle=\"yes\">Thhsf1</jats:italic>\n                      -silenced\n                      <jats:italic toggle=\"yes\">T. hirsuta</jats:italic>\n                      AH28-2 transformants in response to Cu\n                      <jats:sup>2+</jats:sup>\n                      stress.\n                      <jats:italic toggle=\"yes\">Thhsf1</jats:italic>\n                      silencing resulted in downregulated transcriptional levels and activities of LacA, LacB, and LacF, but not LacC. EMSA assays further demonstrated the binding of\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1 only to the promoter regions of\n                      <jats:italic toggle=\"yes\">lacA</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">lacB,</jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">lacF</jats:italic>\n                      containing HSE elements like CTTGAA. A previously reported Hsp70 homolog,\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HspA1, could interact with\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1 and synergistically regulate the expressions of three laccase isozymes.\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1 and\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HspA1 co-overexpression led to approximately 1.5-fold increased laccase activities, providing an efficient strategy to enhance laccase production.\n                    </jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE</jats:title>\n                      <jats:p>\n                        White-rot fungi, especially\n                        <jats:italic toggle=\"yes\">Trametes</jats:italic>\n                        species, are important producers of laccase. They typically express multiple laccase isozymes with distinct physicochemical properties in response to Cu\n                        <jats:sup>2+</jats:sup>\n                        . Elucidating the molecular mechanisms underlying differential laccase expression induced by Cu\n                        <jats:sup>2+</jats:sup>\n                        is critical for enhancing laccase production through strain modification. This study demonstrates that\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HSF1 collaborates with\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HspA1 to regulate the expression of only three Cu\n                        <jats:sup>2+</jats:sup>\n                        -responsive laccase isozymes in\n                        <jats:italic toggle=\"yes\">T. hirsuta</jats:italic>\n                        AH28-2. Co-overexpression of\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HSF1/\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HspA1 efficiently promotes laccase production. These findings also deepen our understanding of how white-rot fungi adapt to environmental Cu\n                        <jats:sup>2+</jats:sup>\n                        .\n                      </jats:p>\n                    </jats:sec>\n                  </jats:sec>","journal":"Microbiology Spectrum","year":2026,"id":630649,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"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":521133,"name":"Rong Zhu","orcid":"0000-0003-4019-8587","position":1,"is_corresponding":false},{"id":1105631,"name":"Shiwen Zhao","orcid":"0000-0001-5750-024X","position":2,"is_corresponding":false},{"id":1633871,"name":"Chenkai Wang","orcid":null,"position":3,"is_corresponding":false},{"id":1633872,"name":"Xinlei Zhang","orcid":"0009-0000-6338-4281","position":4,"is_corresponding":false},{"id":1633874,"name":"Shenglong Liu","orcid":"0009-0009-9916-7903","position":5,"is_corresponding":false},{"id":1633875,"name":"Zemin Fang","orcid":"0000-0002-9853-5470","position":6,"is_corresponding":false},{"id":1589836,"name":"Yazhong Xiao","orcid":"0000-0003-2664-742X","position":7,"is_corresponding":false},{"id":890664,"name":"Juanjuan Liu","orcid":"0000-0002-1062-4488","position":8,"is_corresponding":false},{"id":828400,"name":"Kun Wu","orcid":"0000-0002-1626-396X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Deciphering the role of\n                    <i>Th</i>\n                    HSF1 in the differential expression regulation of laccase isozymes in the white-rot fungus\n                    <i>Trametes hirsuta</i>","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title/>\n                    <jats:p>\n                      White-rot fungi exhibit responses to Cu\n                      <jats:sup>2+</jats:sup>\n                      , leading to a substantial increase in the production of certain laccase isozymes for industry utilization. Currently, studies on the differential expression mechanism of the laccase isozymes in white-rot fungi are limited. Three laccase isozymes, LacA, LacB, and LacF, were significantly induced in\n                      <jats:italic toggle=\"yes\">Trametes hirsuta</jats:italic>\n                      AH28-2 when exposed to Cu\n                      <jats:sup>2+</jats:sup>\n                      , accompanied by a slight enhancement in the isozyme LacC level. Here, based on transcriptomics and proteomics, a nuclear-localized heat shock transcription factor,\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1, was mined and exhibited as a copper-responsive protein involved in the differential regulation of laccase isozyme expression. A changed colony morphology and curved hyphal morphology were observed in three\n                      <jats:italic toggle=\"yes\">Thhsf1</jats:italic>\n                      -silenced\n                      <jats:italic toggle=\"yes\">T. hirsuta</jats:italic>\n                      AH28-2 transformants in response to Cu\n                      <jats:sup>2+</jats:sup>\n                      stress.\n                      <jats:italic toggle=\"yes\">Thhsf1</jats:italic>\n                      silencing resulted in downregulated transcriptional levels and activities of LacA, LacB, and LacF, but not LacC. EMSA assays further demonstrated the binding of\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1 only to the promoter regions of\n                      <jats:italic toggle=\"yes\">lacA</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">lacB,</jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">lacF</jats:italic>\n                      containing HSE elements like CTTGAA. A previously reported Hsp70 homolog,\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HspA1, could interact with\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1 and synergistically regulate the expressions of three laccase isozymes.\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HSF1 and\n                      <jats:italic toggle=\"yes\">Th</jats:italic>\n                      HspA1 co-overexpression led to approximately 1.5-fold increased laccase activities, providing an efficient strategy to enhance laccase production.\n                    </jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE</jats:title>\n                      <jats:p>\n                        White-rot fungi, especially\n                        <jats:italic toggle=\"yes\">Trametes</jats:italic>\n                        species, are important producers of laccase. They typically express multiple laccase isozymes with distinct physicochemical properties in response to Cu\n                        <jats:sup>2+</jats:sup>\n                        . Elucidating the molecular mechanisms underlying differential laccase expression induced by Cu\n                        <jats:sup>2+</jats:sup>\n                        is critical for enhancing laccase production through strain modification. This study demonstrates that\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HSF1 collaborates with\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HspA1 to regulate the expression of only three Cu\n                        <jats:sup>2+</jats:sup>\n                        -responsive laccase isozymes in\n                        <jats:italic toggle=\"yes\">T. hirsuta</jats:italic>\n                        AH28-2. Co-overexpression of\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HSF1/\n                        <jats:italic toggle=\"yes\">Th</jats:italic>\n                        HspA1 efficiently promotes laccase production. These findings also deepen our understanding of how white-rot fungi adapt to environmental Cu\n                        <jats:sup>2+</jats:sup>\n                        .\n                      </jats:p>\n                    </jats:sec>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41288070","pmcid":"PMC12772356","openalex_id":"https://openalex.org/W4416673101","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"32470122","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"U22A20442","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"32370133","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFC2103000","title":null},{"funder_name":"Natural Science Foundation of Anhui Province","grant_id":"2508085Y011","title":null}],"total_grants":5,"fwci":0.9155,"citation_percentile":0.81518582,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1128/spectrum.01004-25","host_type":"journal"},{"url":"https://doi.org/10.1128/spectrum.01004-25","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/spectrum.01004-25","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41288070","host_type":"repository"},{"url":"https://doaj.org/article/ad1d764df45f4c9b987616c83fd998a5","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12772356/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12772356","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12772356?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Enzyme-mediated dye degradation","Fungal and yeast genetics research","melanin and skin pigmentation","Laccase","Gene Expression Regulation, Fungal","Copper","Fungal Proteins","Isoenzymes","Trametes","Heat Shock Transcription Factors"],"mesh_terms":["Heat Shock Transcription Factors","Copper","Fungal Proteins","Isoenzymes","Gene Expression Regulation, Fungal","Laccase","Trametes"],"keywords":["Laccase","Isozyme","Enzyme","Hsp70","Gene expression","Gene silencing","Transcription (linguistics)","heat shock transcription factor","copper stress","Differential Regulation","Laccase Isozyme"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T21:52:13.645131Z","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":[]}