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Front Microbiol. 2016 May 9;7:645. doi: 10.3389/fmicb.2016.00645. eCollection 2016.

A Network of Paralogous Stress Response Transcription Factors in the Human Pathogen Candida glabrata.

Author information

1
Laboratoire de Biologie Computationnelle et Quantitative, Centre National de la Recherche Scientifique, Institut de Biologie Paris-Seine, UMR 7238, Sorbonne Universités, Université Pierre et Marie Curie Paris, France.
2
École Normale Supérieure, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Biologie de l'École Normale Supérieure, Plateforme Génomique Paris, France.
3
Centre National de la Recherche Scientifique, UMR 7592, Institut Jacques Monod, Université Paris Diderot, Sorbonne Paris Cité Paris, France.
4
Évolution, Centre National de la Recherche Scientifique, Institut de Biologie Paris-Seine, UMR 7138, Sorbonne Universités, Université Pierre et Marie Curie Paris, France.

Abstract

The yeast Candida glabrata has become the second cause of systemic candidemia in humans. However, relatively few genome-wide studies have been conducted in this organism and our knowledge of its transcriptional regulatory network is quite limited. In the present work, we combined genome-wide chromatin immunoprecipitation (ChIP-seq), transcriptome analyses, and DNA binding motif predictions to describe the regulatory interactions of the seven Yap (Yeast AP1) transcription factors of C. glabrata. We described a transcriptional network containing 255 regulatory interactions and 309 potential target genes. We predicted with high confidence the preferred DNA binding sites for 5 of the 7 CgYaps and showed a strong conservation of the Yap DNA binding properties between S. cerevisiae and C. glabrata. We provided reliable functional annotation for 3 of the 7 Yaps and identified for Yap1 and Yap5 a core regulon which is conserved in S. cerevisiae, C. glabrata, and C. albicans. We uncovered new roles for CgYap7 in the regulation of iron-sulfur cluster biogenesis, for CgYap1 in the regulation of heme biosynthesis and for CgYap5 in the repression of GRX4 in response to iron starvation. These transcription factors define an interconnected transcriptional network at the cross-roads between redox homeostasis, oxygen consumption, and iron metabolism.

KEYWORDS:

ChIP-seq; Yap; evolution; regulatory networks; transcriptome; yeast

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