Yap7 is a transcriptional repressor of nitric oxide oxidase in yeasts, which arose from neofunctionalization after whole genome duplication.
Flavohemoglobins are the main detoxifiers of nitric oxide (NO) in bacteria and fungi and are induced in response to nitrosative stress. In fungi, the flavohemoglobin encoding gene YHB1 is positively regulated by transcription factors which are activated upon NO exposure. In this study, we show that in the model yeast Saccharomyces cerevisiae and in the human pathogen Candida glabrata, the transcription factor Yap7 constitutively represses YHB1 by binding its promoter. Consequently, YAP7 deletion conferred high NO resistance to the cells. Co-immunoprecipitation experiments and mutant analyses indicated that Yap7 represses YHB1 by recruiting the transcriptional repressor Tup1. In S. cerevisiae, YHB1 repression also involves interaction of Yap7 with the Hap2/3/5 complex through a conserved Hap4-like-bZIP domain, but this interaction has been lost in C. glabrata. The evolutionary origin of this regulation was investigated by functional analyses of Yap7 and of its paralogue Yap5 in different yeast species. These analyses indicated that the negative regulation of YHB1 by Yap7 arose by neofunctionalization after the whole genome duplication which led to the C. glabrata and S. cerevisiae extant species. This work describes a new aspect of the regulation of fungal nitric oxidase and provides detailed insights into its functioning and evolution.
Sorbonne Universités, UPMC Univ. Paris 06, Institut de Biologie Paris Seine UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.|CNRS, UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.
Jawad
J
Merhej
Sorbonne Universités, UPMC Univ. Paris 06, Institut de Biologie Paris Seine UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.|CNRS, UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.
Thierry
T
Delaveau
Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l'hôpital, F-75013, Paris, France.|Inserm, U1135, CIMI-Paris, 91 Bd de l'hôpital, F-75013, Paris, France.|Assistance Publique-Hôpitaux de Paris, Hôpital St Antoine, Service de Parasitologie-Mycologie, F-75012, Paris, France.|CNRS, ERL 8255, CIMI-Paris, 91 Bd de l'hôpital, F-75013, Paris, France.
Juliette
J
Guitard
Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité, F-75205, Paris, France.
Benoit
B
Palancade
Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l'hôpital, F-75013, Paris, France.|Inserm, U1135, CIMI-Paris, 91 Bd de l'hôpital, F-75013, Paris, France.|Assistance Publique-Hôpitaux de Paris, Hôpital St Antoine, Service de Parasitologie-Mycologie, F-75012, Paris, France.|CNRS, ERL 8255, CIMI-Paris, 91 Bd de l'hôpital, F-75013, Paris, France.
Christophe
C
Hennequin
Sorbonne Universités, UPMC Univ. Paris 06, Institut de Biologie Paris Seine UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.|CNRS, UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.
Mathilde
M
Garcia
Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité, F-75205, Paris, France.
Gaëlle
G
Lelandais
Sorbonne Universités, UPMC Univ. Paris 06, Institut de Biologie Paris Seine UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.|CNRS, UMR 7238, Laboratoire de biologie computationnelle et quantitative, F-75006, Paris, France.
Frédéric
F
Devaux
D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000502:physiology; D041221:Candida glabrata / Q000235:genetics*; D049308:Dioxygenases / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020440:Gene Duplication; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D006420:Hemeproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; D006420:Hemeproteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; C000605005:YAP7 protein, S cerevisiae; C526591:Yap5 protein, S cerevisiae; D009569:Nitric Oxide; D049308:Dioxygenases; C101796:YHB1 protein, S cerevisiae