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A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus

Secondary metabolites are produced by numerous organisms and can either be beneficial, benign, or harmful to humans. Genes involved in the synthesis and transport of these secondary metabolites are frequently found in gene clusters, which are often coordinately regulated, being almost exclusively de...

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Autores principales: Schoberle, Taylor J., Nguyen-Coleman, C. Kim, Herold, Jennifer, Yang, Ally, Weirauch, Matt, Hughes, Timothy R., McMurray, John S., May, Gregory S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006717/
https://www.ncbi.nlm.nih.gov/pubmed/24784729
http://dx.doi.org/10.1371/journal.pgen.1004336
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author Schoberle, Taylor J.
Nguyen-Coleman, C. Kim
Herold, Jennifer
Yang, Ally
Weirauch, Matt
Hughes, Timothy R.
McMurray, John S.
May, Gregory S.
author_facet Schoberle, Taylor J.
Nguyen-Coleman, C. Kim
Herold, Jennifer
Yang, Ally
Weirauch, Matt
Hughes, Timothy R.
McMurray, John S.
May, Gregory S.
author_sort Schoberle, Taylor J.
collection PubMed
description Secondary metabolites are produced by numerous organisms and can either be beneficial, benign, or harmful to humans. Genes involved in the synthesis and transport of these secondary metabolites are frequently found in gene clusters, which are often coordinately regulated, being almost exclusively dependent on transcription factors that are located within the clusters themselves. Gliotoxin, which is produced by a variety of Aspergillus species, Trichoderma species, and Penicillium species, exhibits immunosuppressive properties and has therefore been the subject of research for many laboratories. There have been a few proteins shown to regulate the gliotoxin cluster, most notably GliZ, a Zn(2)Cys(6) binuclear finger transcription factor that lies within the cluster, and LaeA, a putative methyltransferase that globally regulates secondary metabolism clusters within numerous fungal species. Using a high-copy inducer screen in A. fumigatus, our lab has identified a novel C(2)H(2) transcription factor, which plays an important role in regulating the gliotoxin biosynthetic cluster. This transcription factor, named GipA, induces gliotoxin production when present in extra copies. Furthermore, loss of gipA reduces gliotoxin production significantly. Through protein binding microarray and mutagenesis, we have identified a DNA binding site recognized by GipA that is in extremely close proximity to a potential GliZ DNA binding site in the 5′ untranslated region of gliA, which encodes an efflux pump within the gliotoxin cluster. Not surprisingly, GliZ and GipA appear to work in an interdependent fashion to positively control gliA expression.
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spelling pubmed-40067172014-05-09 A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus Schoberle, Taylor J. Nguyen-Coleman, C. Kim Herold, Jennifer Yang, Ally Weirauch, Matt Hughes, Timothy R. McMurray, John S. May, Gregory S. PLoS Genet Research Article Secondary metabolites are produced by numerous organisms and can either be beneficial, benign, or harmful to humans. Genes involved in the synthesis and transport of these secondary metabolites are frequently found in gene clusters, which are often coordinately regulated, being almost exclusively dependent on transcription factors that are located within the clusters themselves. Gliotoxin, which is produced by a variety of Aspergillus species, Trichoderma species, and Penicillium species, exhibits immunosuppressive properties and has therefore been the subject of research for many laboratories. There have been a few proteins shown to regulate the gliotoxin cluster, most notably GliZ, a Zn(2)Cys(6) binuclear finger transcription factor that lies within the cluster, and LaeA, a putative methyltransferase that globally regulates secondary metabolism clusters within numerous fungal species. Using a high-copy inducer screen in A. fumigatus, our lab has identified a novel C(2)H(2) transcription factor, which plays an important role in regulating the gliotoxin biosynthetic cluster. This transcription factor, named GipA, induces gliotoxin production when present in extra copies. Furthermore, loss of gipA reduces gliotoxin production significantly. Through protein binding microarray and mutagenesis, we have identified a DNA binding site recognized by GipA that is in extremely close proximity to a potential GliZ DNA binding site in the 5′ untranslated region of gliA, which encodes an efflux pump within the gliotoxin cluster. Not surprisingly, GliZ and GipA appear to work in an interdependent fashion to positively control gliA expression. Public Library of Science 2014-05-01 /pmc/articles/PMC4006717/ /pubmed/24784729 http://dx.doi.org/10.1371/journal.pgen.1004336 Text en © 2014 Schoberle et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Schoberle, Taylor J.
Nguyen-Coleman, C. Kim
Herold, Jennifer
Yang, Ally
Weirauch, Matt
Hughes, Timothy R.
McMurray, John S.
May, Gregory S.
A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus
title A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus
title_full A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus
title_fullStr A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus
title_full_unstemmed A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus
title_short A Novel C(2)H(2) Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus
title_sort novel c(2)h(2) transcription factor that regulates glia expression interdependently with gliz in aspergillus fumigatus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006717/
https://www.ncbi.nlm.nih.gov/pubmed/24784729
http://dx.doi.org/10.1371/journal.pgen.1004336
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