{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:16:53Z","timestamp":1785428213697,"version":"3.56.0"},"reference-count":109,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Science Foundation","award":["CAREER 2041395"],"award-info":[{"award-number":["CAREER 2041395"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The early-branching eukaryotic parasite,\n                      <jats:italic toggle=\"yes\">Trypanosoma brucei<\/jats:italic>\n                      , lives extracellularly in the mammalian host, where it expresses variant surface glycoprotein (VSG). Antigenic variation of VSGs allows the parasite to evade the host immune response while in the bloodstream. Upon transition to the tsetse fly vector, the parasite remodels its surface to express procyclin protein from a limited set of\n                      <jats:italic toggle=\"yes\">EP<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">GPEET<\/jats:italic>\n                      genes. While the environmental signals that trigger the switch from expressing\n                      <jats:italic toggle=\"yes\">VSG<\/jats:italic>\n                      genes to expressing\n                      <jats:italic toggle=\"yes\">EP<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">GPEET<\/jats:italic>\n                      genes are known, the molecular mechanism that initiates transcription of the\n                      <jats:italic toggle=\"yes\">EP<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">GPEET<\/jats:italic>\n                      genes during parasite differentiation to the procyclic stage within the tsetse is not well understood. Previous work has shown that the chromatin-interacting bromodomain protein Bdf3 is absent from the RNA polymerase I promoter of the\n                      <jats:italic toggle=\"yes\">EP<\/jats:italic>\n                      locus in bloodstream parasites, but appears there shortly after initiation of differentiation from the bloodstream to the procyclic stage. Here, we show that tethering of Bdf3 to the\n                      <jats:italic toggle=\"yes\">EP<\/jats:italic>\n                      promoter using a dCas9-Bdf3 fusion protein and a guide RNA is sufficient to increase transcript levels of\n                      <jats:italic toggle=\"yes\">EP1<\/jats:italic>\n                      in bloodstream parasites, where the gene is normally silenced. This result supports the model that Bdf3 appears at the\n                      <jats:italic toggle=\"yes\">EP<\/jats:italic>\n                      locus during differentiation to facilitate initiation of transcription, which is consistent with the role of Bdf3 as a transcriptional activator in other systems. Understanding gene regulatory mechanisms in this early-branching eukaryote may help build a more complete picture of the conserved and unique features of gene regulatory proteins across diverse biological systems.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic toggle=\"yes\">Trypanosoma brucei<\/jats:italic>\n                      parasite is transmitted via the tsetse fly vector to a mammalian host , where it causes African trypanosomiasis, a fatal disease that imposes a severe human and economic burden for people living in areas of sub-Saharan Africa. While drug treatments have improved for some strains, some infections still require treatment with drugs that have serious side effects. One avenue for drug development is to try to manipulate the life cycle of the parasite to make it poorly adapted to the mammalian host. However, this requires detailed knowledge of the mechanisms by which parasites regulate their genes as they progress through the life cycle. Here, we show that the DNA-interacting bromodomain protein Bdf3 may be a key driver for turning on insect-specific genes that code for insect-stage surface proteins. This finding could aid in the development of life cycle-manipulating drugs and shed light on how gene regulatory mechanisms evolved.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00021-26","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:00:59Z","timestamp":1780318859000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The bromodomain protein Bdf3 is sufficient to activate expression of a procyclin gene in bloodstream stage African trypanosomes"],"prefix":"10.1128","volume":"11","author":[{"given":"Evan J.","family":"Kim","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/025ecfn45","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Harvey Mudd College","place":["Claremont, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan 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