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Functional study of the Hap4-like genes suggests that the key regulators of carbon metabolism HAP4 and oxidative stress response YAP1 in yeast diverged from a common ancestor.
PLoS One. 2014; 9(12):e112263.Plos

Abstract

The transcriptional regulator HAP4, induced by respiratory substrates, is involved in the balance between fermentation and respiration in S. cerevisiae. We identified putative orthologues of the Hap4 protein in all ascomycetes, based only on a conserved sixteen amino acid-long motif. In addition to this motif, some of these proteins contain a DNA-binding motif of the bZIP type, while being nonetheless globally highly divergent. The genome of the yeast Hansenula polymorpha contains two HAP4-like genes encoding the protein HpHap4-A which, like ScHap4, is devoid of a bZIP motif, and HpHap4-B which contains it. This species has been chosen for a detailed examination of their respective properties. Based mostly on global gene expression studies performed in the S. cerevisiae HAP4 disruption mutant (ScΔhap4), we show here that HpHap4-A is functionally equivalent to ScHap4, whereas HpHap4-B is not. Moreover HpHAP4-B is able to complement the H2O2 hypersensitivity of the ScYap1 deletant, YAP1 being, in S. cerevisiae, the main regulator of oxidative stress. Finally, a transcriptomic analysis performed in the ScΔyap1 strain overexpressing HpHAP4-B shows that HpHap4-B acts both on oxidative stress response and carbohydrate metabolism in a manner different from both ScYap1 and ScHap4. Deletion of these two genes in their natural host, H. polymorpha, confirms that HpHAP4-A participates in the control of the fermentation/respiration balance, while HpHAP4-B is involved in oxidative stress since its deletion leads to hypersensitivity to H2O2. These data, placed in an evolutionary context, raise new questions concerning the evolution of the HAP4 transcriptional regulation function and suggest that Yap1 and Hap4 have diverged from a unique regulatory protein in the fungal ancestor.

Authors+Show Affiliations

Institut de Génétique et Microbiologie, IFR Génome 115, Université Paris-Sud and CNRS, Orsay, France; Institute of Cell Biology, National Academy of Sciences, Lviv, Ukraine; Centre de Génétique Moléculaire, CNRS, Gif sur Yvette, France.Institut de Génétique et Microbiologie, IFR Génome 115, Université Paris-Sud and CNRS, Orsay, France.Institut de Génétique et Microbiologie, IFR Génome 115, Université Paris-Sud and CNRS, Orsay, France.Gif/Orsay DNA MicroArray Platform, Gif sur Yvette, France; Centre de Génétique Moléculaire, CNRS, Gif sur Yvette, France.Centre de Génétique Moléculaire, CNRS, Gif sur Yvette, France.Institut de Génétique et Microbiologie, IFR Génome 115, Université Paris-Sud and CNRS, Orsay, France.Institute of Cell Biology, National Academy of Sciences, Lviv, Ukraine.Institute of Cell Biology, National Academy of Sciences, Lviv, Ukraine; Department of Biochemistry, Ivan Franko Lviv National University, Lviv, Ukraine.Institute of Cell Biology, National Academy of Sciences, Lviv, Ukraine.Institut de Génétique et Microbiologie, IFR Génome 115, Université Paris-Sud and CNRS, Orsay, France; Gif/Orsay DNA MicroArray Platform, Gif sur Yvette, France.Gif/Orsay DNA MicroArray Platform, Gif sur Yvette, France; Centre de Génétique Moléculaire, CNRS, Gif sur Yvette, France.Gif/Orsay DNA MicroArray Platform, Gif sur Yvette, France.Gif/Orsay DNA MicroArray Platform, Gif sur Yvette, France.Gif/Orsay DNA MicroArray Platform, Gif sur Yvette, France; Centre de Génétique Moléculaire, CNRS, Gif sur Yvette, France.Institute of Cell Biology, National Academy of Sciences, Lviv, Ukraine; University of Rzeszow, Rzeszow, Poland.Institut de Génétique et Microbiologie, IFR Génome 115, Université Paris-Sud and CNRS, Orsay, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25479159

Citation

Petryk, Nataliya, et al. "Functional Study of the Hap4-like Genes Suggests That the Key Regulators of Carbon Metabolism HAP4 and Oxidative Stress Response YAP1 in Yeast Diverged From a Common Ancestor." PloS One, vol. 9, no. 12, 2014, pp. e112263.
Petryk N, Zhou YF, Sybirna K, et al. Functional study of the Hap4-like genes suggests that the key regulators of carbon metabolism HAP4 and oxidative stress response YAP1 in yeast diverged from a common ancestor. PLoS One. 2014;9(12):e112263.
Petryk, N., Zhou, Y. F., Sybirna, K., Mucchielli, M. H., Guiard, B., Bao, W. G., Stasyk, O. V., Stasyk, O. G., Krasovska, O. S., Budin, K., Reymond, N., Imbeaud, S., Coudouel, S., Delacroix, H., Sibirny, A., & Bolotin-Fukuhara, M. (2014). Functional study of the Hap4-like genes suggests that the key regulators of carbon metabolism HAP4 and oxidative stress response YAP1 in yeast diverged from a common ancestor. PloS One, 9(12), e112263. https://doi.org/10.1371/journal.pone.0112263
Petryk N, et al. Functional Study of the Hap4-like Genes Suggests That the Key Regulators of Carbon Metabolism HAP4 and Oxidative Stress Response YAP1 in Yeast Diverged From a Common Ancestor. PLoS One. 2014;9(12):e112263. PubMed PMID: 25479159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional study of the Hap4-like genes suggests that the key regulators of carbon metabolism HAP4 and oxidative stress response YAP1 in yeast diverged from a common ancestor. AU - Petryk,Nataliya, AU - Zhou,You-Fang, AU - Sybirna,Kateryna, AU - Mucchielli,Marie-Hélène, AU - Guiard,Bernard, AU - Bao,Wei-Guo, AU - Stasyk,Oleh V, AU - Stasyk,Olena G, AU - Krasovska,Olena S, AU - Budin,Karine, AU - Reymond,Nancie, AU - Imbeaud,Sandrine, AU - Coudouel,Sophie, AU - Delacroix,Hervé, AU - Sibirny,Andriy, AU - Bolotin-Fukuhara,Monique, Y1 - 2014/12/05/ PY - 2014/03/12/received PY - 2014/10/06/accepted PY - 2014/12/6/entrez PY - 2014/12/6/pubmed PY - 2015/7/30/medline SP - e112263 EP - e112263 JF - PloS one JO - PLoS One VL - 9 IS - 12 N2 - The transcriptional regulator HAP4, induced by respiratory substrates, is involved in the balance between fermentation and respiration in S. cerevisiae. We identified putative orthologues of the Hap4 protein in all ascomycetes, based only on a conserved sixteen amino acid-long motif. In addition to this motif, some of these proteins contain a DNA-binding motif of the bZIP type, while being nonetheless globally highly divergent. The genome of the yeast Hansenula polymorpha contains two HAP4-like genes encoding the protein HpHap4-A which, like ScHap4, is devoid of a bZIP motif, and HpHap4-B which contains it. This species has been chosen for a detailed examination of their respective properties. Based mostly on global gene expression studies performed in the S. cerevisiae HAP4 disruption mutant (ScΔhap4), we show here that HpHap4-A is functionally equivalent to ScHap4, whereas HpHap4-B is not. Moreover HpHAP4-B is able to complement the H2O2 hypersensitivity of the ScYap1 deletant, YAP1 being, in S. cerevisiae, the main regulator of oxidative stress. Finally, a transcriptomic analysis performed in the ScΔyap1 strain overexpressing HpHAP4-B shows that HpHap4-B acts both on oxidative stress response and carbohydrate metabolism in a manner different from both ScYap1 and ScHap4. Deletion of these two genes in their natural host, H. polymorpha, confirms that HpHAP4-A participates in the control of the fermentation/respiration balance, while HpHAP4-B is involved in oxidative stress since its deletion leads to hypersensitivity to H2O2. These data, placed in an evolutionary context, raise new questions concerning the evolution of the HAP4 transcriptional regulation function and suggest that Yap1 and Hap4 have diverged from a unique regulatory protein in the fungal ancestor. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25479159/Functional_study_of_the_Hap4_like_genes_suggests_that_the_key_regulators_of_carbon_metabolism_HAP4_and_oxidative_stress_response_YAP1_in_yeast_diverged_from_a_common_ancestor_ DB - PRIME DP - Unbound Medicine ER -