This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hach, A.
Right arrow Articles by Zhang, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hach, A.
Right arrow Articles by Zhang, L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 1999, p. 4324-4333, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A New Class of Repression Modules Is Critical for Heme Regulation of the Yeast Transcriptional Activator Hap1

Angela Hach, Thomas Hon, and Li Zhang*

Department of Biochemistry, NYU Medical Center, New York, New York 10016

Received 18 December 1998/Returned for modification 8 February 1999/Accepted 24 March 1999

Heme plays key regulatory roles in numerous molecular and cellular processes for systems that sense or use oxygen. In the yeast Saccharomyces cerevisiae, oxygen sensing and heme signaling are mediated by heme activator protein 1 (Hap1). Hap1 contains seven heme-responsive motifs (HRMs): six are clustered in the heme domain, and a seventh is near the activation domain. To determine the functional role of HRMs and to define which parts of Hap1 mediate heme regulation, we carried out a systematic analysis of Hap1 mutants with various regions deleted or mutated. Strikingly, the data show that HRM1 to -6, located in the previously designated Hap1 heme domain, have little impact on heme regulation. All seven HRMs are dispensable for Hap1 repression in the absence of heme, but HRM7 is required for Hap1 activation by heme. More importantly, we show that a novel class of repression modules---RPM1, encompassing residues 245 to 278; RPM2, encompassing residues 1061 to 1185; and RPM3, encompassing residues 203 to 244---is critical for Hap1 repression in the absence of heme. Biochemical analysis indicates that RPMs mediate Hap1 repression, at least partly, by the formation of a previously identified higher-order complex termed the high-molecular-weight complex (HMC), while HRMs mediate heme activation by permitting heme binding and the disassembly of the HMC. These findings provide significant new insights into the molecular interactions critical for Hap1 repression in the absence of heme and Hap1 activation by heme.

* Corresponding author. Mailing address: Department of Biochemistry, NYU Medical Center, 550 First Ave., New York, NY 10016. Phone: (212) 263-8506. Fax: (212) 263-8166. E-mail: zhang102{at}mcrcr0.med.nyu.edu.

Molecular and Cellular Biology, June 1999, p. 4324-4333, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Shahi, P., Gulshan, K., Moye-Rowley, W. S. (2007). Negative Transcriptional Regulation of Multidrug Resistance Gene Expression by an Hsp70 Protein. J. Biol. Chem. 282: 26822-26831 [Abstract] [Full Text]  
  • Hon, T., Lee, H. C., Hu, Z., Iyer, V. R., Zhang, L. (2005). The Heme Activator Protein Hap1 Represses Transcription by a Heme-Independent Mechanism in Saccharomyces cerevisiae. Genetics 169: 1343-1352 [Abstract] [Full Text]  
  • Lan, C., Lee, H. C., Tang, S., Zhang, L. (2004). A Novel Mode of Chaperone Action: HEME ACTIVATION OF Hap1 BY ENHANCED ASSOCIATION OF Hsp90 WITH THE REPRESSED Hsp70-Hap1 COMPLEX. J. Biol. Chem. 279: 27607-27612 [Abstract] [Full Text]  
  • Hon, T., Dodd, A., Dirmeier, R., Gorman, N., Sinclair, P. R., Zhang, L., Poyton, R. O. (2003). A Mechanism of Oxygen Sensing in Yeast: MULTIPLE OXYGEN-RESPONSIVE STEPS IN THE HEME BIOSYNTHETIC PATHWAY AFFECT Hap1 ACTIVITY. J. Biol. Chem. 278: 50771-50780 [Abstract] [Full Text]  
  • Lee, H. C., Hon, T., Lan, C., Zhang, L. (2003). Structural Environment Dictates the Biological Significance of Heme-Responsive Motifs and the Role of Hsp90 in the Activation of the Heme Activator Protein Hap1. Mol. Cell. Biol. 23: 5857-5866 [Abstract] [Full Text]  
  • Xu, H., Wu, P., Wu, C. F. J., Tidwell, C., Wang, Y. (2002). A smooth response surface algorithm for constructing a gene regulatory network. Physiol. Genomics 11: 11-20 [Abstract] [Full Text]  
  • Panek, H., O'Brian, M. R. (2002). A whole genome view of prokaryotic haem biosynthesis. Microbiology 148: 2273-2282 [Full Text]  
  • Lee, H. C., Hon, T., Zhang, L. (2002). The Molecular Chaperone Hsp90 Mediates Heme Activation of the Yeast Transcriptional Activator Hap1. J. Biol. Chem. 277: 7430-7437 [Abstract] [Full Text]  
  • Hon, T., Lee, H. C., Hach, A., Johnson, J. L., Craig, E. A., Erdjument-Bromage, H., Tempst, P., Zhang, L. (2001). The Hsp70-Ydj1 Molecular Chaperone Represses the Activity of the Heme Activator Protein Hap1 in the Absence of Heme. Mol. Cell. Biol. 21: 7923-7932 [Abstract] [Full Text]  
  • Vik, A., Rine, J. (2001). Upc2p and Ecm22p, Dual Regulators of Sterol Biosynthesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 21: 6395-6405 [Abstract] [Full Text]  
  • WOOLF, P. J., WANG, Y. (2000). A fuzzy logic approach to analyzing gene expression data. Physiol. Genomics 3: 9-15 [Abstract] [Full Text]  
  • Hach, A., Hon, T., Zhang, L. (2000). The Coiled Coil Dimerization Element of the Yeast Transcriptional Activator Hap1, a Gal4 Family Member, Is Dispensable for DNA Binding but Differentially Affects Transcriptional Activation. J. Biol. Chem. 275: 248-254 [Abstract] [Full Text]  
  • Zhang, X., Cui, Z., Miyakawa, T., Moye-Rowley, W. S. (2001). Cross-talk between Transcriptional Regulators of Multidrug Resistance in Saccharomyces cerevisiae. J. Biol. Chem. 276: 8812-8819 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»