A novel C2H2 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 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 Zn2Cys6 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 C2H2 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.
The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Taylor J
TJ
Schoberle
The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
C Kim
CK
Nguyen-Coleman
The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; Microbiology and Molecular Genetics, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Jennifer
J
Herold
Banting and Best Department of Medical Research, Donnelly Centre, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Ally
A
Yang
Banting and Best Department of Medical Research, Donnelly Centre, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Matt
M
Weirauch
Banting and Best Department of Medical Research, Donnelly Centre, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Timothy R
TR
Hughes
The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
John S
JS
McMurray
The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; Microbiology and Molecular Genetics, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; Program in Genes and Development, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Gregory S
GS
May
D020121:5' Untranslated Regions; D001232:Aspergillus fumigatus / Q000378:metabolism*; D001665:Binding Sites; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*
D020121:5' Untranslated Regions; D005656:Fungal Proteins; D014157:Transcription Factors