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Eukaryotic Cell, June 2007, p. 1018-1029, Vol. 6, No. 6
1535-9778/07/$08.00+0     doi:10.1128/EC.00078-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Transcriptional Profiling of Cross Pathway Control in Neurospora crassa and Comparative Analysis of the Gcn4 and CPC1 Regulons{triangledown} ,{dagger}

Chaoguang Tian,1 Takao Kasuga,1 Matthew S. Sachs,2 and N. Louise Glass1*

Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California 94720-3102,1 Oregon Health and Science University, Beaverton, Oregon 97006-89212

Received 13 March 2007/ Accepted 16 April 2007

Identifying and characterizing transcriptional regulatory networks is important for guiding experimental tests on gene function. The characterization of regulatory networks allows comparisons among both closely and distantly related species, providing insight into network evolution, which is predicted to correlate with the adaptation of different species to particular environmental niches. One of the most intensely studied regulatory factors in the yeast Saccharomyces cerevisiae is the bZIP transcription factor Gcn4p. Gcn4p is essential for a global transcriptional response when S. cerevisiae experiences amino acid starvation. In the filamentous ascomycete Neurospora crassa, the ortholog of GCN4 is called the cross pathway control-1 (cpc-1) gene; it is required for the ability of N. crassa to induce a number of amino acid biosynthetic genes in response to amino acid starvation. Here, we deciphered the CPC1 regulon by profiling transcription in wild-type and cpc-1 mutant strains with full-genome N. crassa 70-mer oligonucleotide microarrays. We observed that at least 443 genes were direct or indirect CPC1 targets; these included 67 amino acid biosynthetic genes, 16 tRNA synthetase genes, and 13 vitamin-related genes. Comparison among the N. crassa CPC1 transcriptional profiling data set and the Gcn4/CaGcn4 data sets from S. cerevisiae and Candida albicans revealed a conserved regulon of 32 genes, 10 of which are predicted to be directly regulated by Gcn4p/CPC1. The 32-gene conserved regulon comprises mostly amino acid biosynthetic genes. The comparison of regulatory networks in species with clear orthology among genes sheds light on how gene interaction networks evolve.

* Corresponding author. Mailing address: Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720-3102. Phone: (510) 643-2399. Fax: (510) 642-4995. E-mail: Lglass{at}nature.berkeley.edu

{triangledown} Published ahead of print on 20 April 2007.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, June 2007, p. 1018-1029, Vol. 6, No. 6
1535-9778/07/$08.00+0     doi:10.1128/EC.00078-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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