{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:59:57Z","timestamp":1790171997199,"version":"4.1.0"},"reference-count":84,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/01580-7, 2023\/12805-5"],"award-info":[{"award-number":["2021\/01580-7, 2023\/12805-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/14399-1"],"award-info":[{"award-number":["2022\/14399-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/11655-4"],"award-info":[{"award-number":["2019\/11655-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/03766-8"],"award-info":[{"award-number":["2018\/03766-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Trichoderma reesei<\/jats:italic>\n                      is known for its ability to secrete high amounts of cellulases, enzymes of fundamental importance in generating products from lignocellulosic biomass. Diverse signaling pathways and transcription factors (TFs) control the cellulolytic repertoire in\n                      <jats:italic toggle=\"yes\">T. reesei<\/jats:italic>\n                      to ensure correct adaptation to the environment. Here, we analyzed RNA-Seq data and identified a new potential regulator of cellulase production in\n                      <jats:italic toggle=\"yes\">T. reesei<\/jats:italic>\n                      : a novel TF named Nsd3, a homolog of NsdC from\n                      <jats:italic toggle=\"yes\">Aspergilli<\/jats:italic>\n                      . Deletion of\n                      <jats:italic toggle=\"yes\">nsd3<\/jats:italic>\n                      reduced vegetative growth and conidiation on solid medium. Phenotypic characterization of the \u0394\n                      <jats:italic toggle=\"yes\">nsd3<\/jats:italic>\n                      strain showed that it is more sensitive to osmotic stress, but more resistant to cell wall and oxidative stresses. Our results showed that Nsd3 is a repressor of cellulase expression by directly regulating key genes in the cellulolytic pathway, an unreported role for this TF in fungi. Loss of\n                      <jats:italic toggle=\"yes\">nsd3<\/jats:italic>\n                      leads to a faster and more robust induction of cellulolytic genes, and higher cellulase and hemicellulase activities. Transcriptional profiling by RNA-Seq, chromatin accessibility profiling by ATAC-Seq, and protein-DNA interaction assays showed that sugar transporters are important targets of Nsd3 during cellulase expression regulation. Combined with microscopy and gene expression analyses, the ATAC-Seq data also highlighted Nsd3 as a central regulator of cell wall remodeling and organization. Furthermore, the transcriptomics also showed that Nsd3 regulates genes involved in secondary metabolism. These results showed that Nsd3 regulates several physiological processes and provide novel insights into the regulatory system of cellulases in\n                      <jats:italic toggle=\"yes\">T. reesei<\/jats:italic>\n                      that can be used in the design of high-performance strains for biorefinery.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Trichoderma reesei<\/jats:italic>\n                        is a key player in the production of hydrolytic enzymes for the degradation of lignocellulose biomass, and transcription factors are important targets for genetic engineering to construct cellulase-hyperproducing strains. Here, we identified the transcription factor Nsd3 and characterized its role as a regulator of cellulase production in\n                        <jats:italic toggle=\"yes\">T. reesei<\/jats:italic>\n                        . We applied two powerful genomics methods (transcriptome sequencing and chromatin accessibility sequencing) to unravel the global role of Nsd3 and its regulatory mechanism. Nsd3 participates in various biological processes in\n                        <jats:italic toggle=\"yes\">T. reesei<\/jats:italic>\n                        , including cell wall remodeling, calcium metabolism, and secondary metabolism, in addition to regulating the expression of sugar transporters. Protein-DNA interaction assays demonstrate that Nsd3 acts through important genes to regulate cellulase expression, including ace4, crt1, stp1, and cel1b. Our study provides mechanistic insights about how Nsd3 regulates diverse physiological processes in\n                        <jats:italic toggle=\"yes\">T. reesei<\/jats:italic>\n                        . This work also applied ATAC-Seq for the first time to study chromatin accessibility in\n                        <jats:italic toggle=\"yes\">T. reesei<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.00865-26","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:00:49Z","timestamp":1788440449000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Trichoderma reesei<\/i>\n                    Nsd3 transcription factor: pleiotropic roles in development, stress response, secondary metabolism, and cellulase production"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-3083","authenticated-orcid":true,"given":"David Batista","family":"Mau\u00e9s","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo","place":["Ribeir\u00e3o Preto, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Matheus Soares","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo","place":["Ribeir\u00e3o Preto, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2052-2848","authenticated-orcid":true,"given":"Andrei Stecca","family":"Steindorff","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jbv0t02","id-type":"ROR","asserted-by":"publisher"}],"name":"US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Cristina Campos","family":"Antoni\u00eato","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo","place":["Ribeir\u00e3o Preto, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Silva-Rocha","sequence":"additional","affiliation":[{"name":"ByMyCell Inova Simples LTDA","place":["Ribeir\u00e3o Preto, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Dam\u00e1rio","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo","place":["Ribeir\u00e3o Preto, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1735-8266","authenticated-orcid":true,"given":"Zachary A.","family":"Lewis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bjhwk41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8992-7130","authenticated-orcid":true,"given":"Roberto N.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo","place":["Ribeir\u00e3o Preto, Brazil"]},{"id":[{"id":"https:\/\/ror.org\/052a22698","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Science and Technology in Human Pathogenic Fungi","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/gcbb.13130"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13237-024-00501-6"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-020-01732-w"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-019-1571-z"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2859-11-134"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707713114"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389202917666151116212901"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00170-12"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-020-01797-7"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93552-7"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-023-02279-9"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.505826"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00872-22"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00211-06"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010048"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02172374"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-269"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-003-0895-2"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1807-7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14352"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2014.10.009"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00175"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03456-21"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904936106"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","unstructured":"Hinterdobler W Beier S Kindel S Schmoll M. 2020. Sexual development its determinants and regulation in Trichoderma Reesei new and future developments in microbial biotechnology and bioengineering. Elsevier B.V. Available from: http:\/\/dx.doi.org\/10.1016\/B978-0-12-819453-9.00009-X","DOI":"10.1016\/B978-0-12-819453-9.00009-X"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-015-0311-2"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.109.101667"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2015.08.007"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00069-12"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03102-20"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/1754-6834-7-41"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00037-13"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00321118"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12993"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.397"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13334"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.1.53-58.1989"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-022-02230-x"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-013-5354-3"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rser.2020.109991"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-025-13408-2"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi052553y"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2018.09.005"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jobm.202400573"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-023-02371-7"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-016-0564-4"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt890"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp335"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00796-9"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03495-23"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008320"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/ffunb.2022.1002161"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-016-0488-z"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01408-16"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00161-19"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof9121173"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof11090658"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12111544"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072189"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-022-01809-1"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00593-21"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.008497"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099366"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33383-1"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy096"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00256-08"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-539-8_7"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-313x.1999.00487.x"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2009.10.012"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.095"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbad051"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae620"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-021-07774-0"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2688"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7804-5_19"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw257"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr064"}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aem.00865-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aem.00865-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:03:55Z","timestamp":1790168635000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aem.00865-26"}},"subtitle":[],"editor":[{"given":"Yvonne","family":"Nyg\u00e5rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":84,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,23]]}},"alternative-id":["10.1128\/aem.00865-26"],"URL":"https:\/\/doi.org\/10.1128\/aem.00865-26","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"assertion":[{"value":"2026-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00865-26"}}