The Zap1 Transcriptional Activator Also Acts As a Repressor by Binding Downstream of the TATA Box in ZRT2

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2004 Feb 21

PMID 14976557

Citations 45

Authors

Amanda J Bird

Elizabeth Blankman

David J Stillman

David J Eide

Dennis R Winge

Affiliations

Soon will be listed here.

Abstract

The zinc-responsive transcriptional activator Zap1 regulates the expression of both high- and low-affinity zinc uptake permeases encoded by the ZRT1 and ZRT2 genes. Zap1 mediates this response by binding to zinc-responsive elements (ZREs) located within the promoter regions of each gene. ZRT2 has a remarkably different expression profile in response to zinc compared to ZRT1. While ZRT1 is maximally induced during zinc limitation, ZRT2 is repressed in low zinc but remains induced upon zinc supplementation. In this study, we determined the mechanism underlying this paradoxical Zap1-dependent regulation of ZRT2. We demonstrate that a nonconsensus ZRE (ZRT2 ZRE3), which overlaps with one of the ZRT2 transcriptional start sites, is essential for repression of ZRT2 in low zinc and that Zap1 binds to ZRT2 ZRE3 with a low affinity. The low-affinity ZRE is also essential for the ZRT2 expression profile. These results indicate that the unusual pattern of ZRT2 regulation among Zap1 target genes involves the antagonistic effect of Zap1 binding to a low-affinity ZRE repressor site and high-affinity ZREs required for activation.

Citing Articles

Zinc Starvation Induces Cell Wall Remodeling and Activates the Antioxidant Defense System in .

Santos T, Soares L, Oliveira L, Moraes D, Mendes M, Soares C J Fungi (Basel). 2024; 10(2).

PMID: 38392790 PMC: 10890210. DOI: 10.3390/jof10020118.

Global Molecular Response of to Zinc Deprivation: Analyses at Transcript, Protein and MicroRNA Levels.

Mesquita L, Bailao A, Santana de Curcio J, da Silva K, da Rocha Fernandes G, Silva-Bailao M J Fungi (Basel). 2023; 9(3).

PMID: 36983449 PMC: 10056003. DOI: 10.3390/jof9030281.

Zinc homeostasis in Schizosaccharomyces pombe.

Yao R, Li R, Huang Y Arch Microbiol. 2023; 205(4):126.

PMID: 36943461 DOI: 10.1007/s00203-023-03473-4.

Transcriptional Regulation and Protein Localization of Zip10, Zip13 and Zip14 Transporters of Freshwater Teleost Yellow Catfish Following Zn Exposure in a Heterologous HEK293T Model.

Liu S, Xu Y, Tan X, Zhao T, Zhang D, Yang H Int J Mol Sci. 2022; 23(14).

PMID: 35887381 PMC: 9321221. DOI: 10.3390/ijms23148034.

Characterization and functional analysis of zinc trafficking in the human fungal pathogen .

Takacs T, Nemeth M, Bohner F, Vagvolgyi C, Jankovics F, Wilson D Open Biol. 2022; 12(7):220077.

PMID: 35857903 PMC: 9277298. DOI: 10.1098/rsob.220077.

References

Bird A, Evans-Galea M, Blankman E, Zhao H, Luo H, Winge D . Mapping the DNA binding domain of the Zap1 zinc-responsive transcriptional activator. J Biol Chem. 2000; 275(21):16160-6. DOI: 10.1074/jbc.M000664200. View

Kadam S, Emerson B . Mechanisms of chromatin assembly and transcription. Curr Opin Cell Biol. 2002; 14(3):262-8. DOI: 10.1016/s0955-0674(02)00330-7. View

Lyons T, Gasch A, Gaither L, Botstein D, Brown P, Eide D . Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. Proc Natl Acad Sci U S A. 2000; 97(14):7957-62. PMC: 16652. DOI: 10.1073/pnas.97.14.7957. View

Bird A, Zhao H, Luo H, Jensen L, Srinivasan C, Winge D . A dual role for zinc fingers in both DNA binding and zinc sensing by the Zap1 transcriptional activator. EMBO J. 2000; 19(14):3704-13. PMC: 313982. DOI: 10.1093/emboj/19.14.3704. View

Munsterkotter M, Barbaric S, Horz W . Transcriptional regulation of the yeast PHO8 promoter in comparison to the coregulated PHO5 promoter. J Biol Chem. 2000; 275(30):22678-85. DOI: 10.1074/jbc.M001409200. View

Washburn B, Esposito R . Identification of the Sin3-binding site in Ume6 defines a two-step process for conversion of Ume6 from a transcriptional repressor to an activator in yeast. Mol Cell Biol. 2001; 21(6):2057-69. PMC: 86811. DOI: 10.1128/MCB.21.6.2057-2069.2001. View

Rojo F . Mechanisms of transcriptional repression. Curr Opin Microbiol. 2001; 4(2):145-51. DOI: 10.1016/s1369-5274(00)00180-6. View

Lieb J, Liu X, Botstein D, Brown P . Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association. Nat Genet. 2001; 28(4):327-34. DOI: 10.1038/ng569. View

Narlikar G, Fan H, Kingston R . Cooperation between complexes that regulate chromatin structure and transcription. Cell. 2002; 108(4):475-87. DOI: 10.1016/s0092-8674(02)00654-2. View

10.

Barolo S, Posakony J . Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev. 2002; 16(10):1167-81. DOI: 10.1101/gad.976502. View

11.

Proft M, Struhl K . Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress. Mol Cell. 2002; 9(6):1307-17. DOI: 10.1016/s1097-2765(02)00557-9. View

12.

Waters B, Eide D . Combinatorial control of yeast FET4 gene expression by iron, zinc, and oxygen. J Biol Chem. 2002; 277(37):33749-57. DOI: 10.1074/jbc.M206214200. View

13.

MacDiarmid C, Milanick M, Eide D . Biochemical properties of vacuolar zinc transport systems of Saccharomyces cerevisiae. J Biol Chem. 2002; 277(42):39187-94. DOI: 10.1074/jbc.M205052200. View

14.

Lee T, Rinaldi N, Robert F, Odom D, Bar-Joseph Z, Gerber G . Transcriptional regulatory networks in Saccharomyces cerevisiae. Science. 2002; 298(5594):799-804. DOI: 10.1126/science.1075090. View

15.

Evans-Galea M, Blankman E, Myszka D, Bird A, Eide D, Winge D . Two of the five zinc fingers in the Zap1 transcription factor DNA binding domain dominate site-specific DNA binding. Biochemistry. 2003; 42(4):1053-61. DOI: 10.1021/bi0263199. View

16.

MacDiarmid C, Milanick M, Eide D . Induction of the ZRC1 metal tolerance gene in zinc-limited yeast confers resistance to zinc shock. J Biol Chem. 2003; 278(17):15065-72. DOI: 10.1074/jbc.M300568200. View

17.

Zeitlinger J, Simon I, Harbison C, Hannett N, L Volkert T, Fink G . Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling. Cell. 2003; 113(3):395-404. DOI: 10.1016/s0092-8674(03)00301-5. View

18.

Kellis M, Patterson N, Endrizzi M, Birren B, Lander E . Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature. 2003; 423(6937):241-54. DOI: 10.1038/nature01644. View

19.

Cliften P, Sudarsanam P, Desikan A, Fulton L, Fulton B, Majors J . Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science. 2003; 301(5629):71-6. DOI: 10.1126/science.1084337. View

20.

Bird A, McCall K, Kramer M, Blankman E, Winge D, Eide D . Zinc fingers can act as Zn2+ sensors to regulate transcriptional activation domain function. EMBO J. 2003; 22(19):5137-46. PMC: 204467. DOI: 10.1093/emboj/cdg484. View