Hugo Lavoie1,2¤, Hervé Hogues1, Jaideep Mallick1, Adnane Sellam1,3, André Nantel1,3, Malcolm Whiteway1,2*
1 Biotechnology Research Institute, National Research Council, Montreal, Quebec, Canada, 2 Department of Biology, McGill University, Montreal, Quebec, Canada, 3 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada
Abstract
Gene expression variation between species is a major contributor to phenotypic diversity, yet the underlying flexibility of transcriptional regulatory networks remains largely unexplored. Transcription of the ribosomal regulon is a critical task for all cells; in S. cerevisiae the transcription factors Rap1, Fhl1, Ifh1, and Hmo1 form a multi-subunit complex that controls ribosomal gene expression, while in C. albicans this regulation is under the control of Tbf1 and Cbf1. Here, we analyzed, using full-genome transcription factor mapping, the roles, in both S. cerevisiae and C. albicans, of each orthologous component of this complete set of regulators. We observe dramatic changes in the binding profiles of the generalist regulators Cbf1, Hmo1, Rap1, and Tbf1, while the Fhl1-Ifh1 dimer is the only component involved in ribosomal regulation in both fungi: it activates ribosomal protein genes and rDNA expression in a Tbf1-dependent manner in C. albicans and a Rap1-dependent manner in S. cerevisiae. We show that the transcriptional regulatory network governing the ribosomal expression program of two related yeast species has been massively reshaped in cis and trans. Changes occurred in transcription factor wiring with cellular functions, movements in transcription factor hierarchies, DNA-binding specificity, and regulatory complexes assembly to promote global changes in the architecture of the fungal transcriptional regulatory network.
Author Summary
Conserved metabolic machineries direct energy production and investment in most life forms. However, variation in the transcriptional regulation of the genes that encode this machinery has been observed and shown to contribute to phenotypic differences between species. Here, we show that the regulatory circuits governing the expression of central metabolic components (in this case the ribosomes) in different yeast species have an unexpected level of evolutionary plasticity. Most transcription factors involved in the regulation of expression of ribosomal genes have in fact been reused in new ways during the evolutionary time separating S. cerevisiae and C. albicans to generate global changes in transcriptional network structures and new ribosomal regulatory complexes.
Citation: Lavoie H, Hogues H, Mallick J, Sellam A, Nantel A, et al. (2010) Evolutionary Tinkering with Conserved Components of a Transcriptional Regulatory Network. PLoS Biol 8(3): e1000329. doi:10.1371/journal.pbio.1000329
Academic Editor: Kenneth H. Wolfe, Trinity College Dublin, Ireland
Received: August 11, 2009; Accepted: February 3, 2010; Published: March 9, 2010
Copyright: © 2010 Lavoie et al. 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 credited.
Funding: This work was supported by a grant from Canadian Institute for Health Research (CIHR; http://www.cihr-irsc.gc.ca/e/193.html) to MW and AN (MOP-84341). HL was supported by scholarships from CIHR and CNRC and by NCIC (www.cancer.ca/research/) grant 17134 to MW and David Thomas. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: CGD, Candida genome database; ChIP, chromatin immunoprecipitation; GO, gene ontology; RP, ribosomal protein; SGD, Saccharomyces genome database; TF, transcription factor; TRN, transcriptional regulatory network; WCE, whole-cell extract
* E-mail: malcolm.whiteway@cnrc-nrc.gc.ca
¤ Current address: Intracellular Signaling Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, Quebec, Canada.
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