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 Google Scholar
Google Scholar
Right arrow Articles by Mead, J.
Right arrow Articles by Vershon, A. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mead, J.
Right arrow Articles by Vershon, A. K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2007, p. 2466-2475, Vol. 27, No. 7
0270-7306/07/$08.00+0     doi:10.1128/MCB.01641-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Swapping the Gene-Specific and Regional Silencing Specificities of the Hst1 and Sir2 Histone Deacetylases{triangledown}

Janet Mead,1 Ron McCord,1,{dagger} Laura Youngster,1 Mandakini Sharma,2,{ddagger} Marc R. Gartenberg,2 and Andrew K. Vershon1*

Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854,1 Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 088542

Received 2 September 2006/ Returned for modification 9 November 2006/ Accepted 8 January 2007

Sir2 and Hst1 are NAD+-dependent histone deacetylases of budding yeast that are related by strong sequence similarity. Nevertheless, the two proteins promote two mechanistically distinct forms of gene repression. Hst1 interacts with Rfm1 and Sum1 to repress the transcription of specific middle-sporulation genes. Sir2 interacts with Sir3 and Sir4 to silence genes contained within the silent-mating-type loci and telomere chromosomal regions. To identify the determinants of gene-specific versus regional repression, we created a series of Hst1::Sir2 hybrids. Our analysis yielded two dual-specificity chimeras that were able to perform both regional and gene-specific repression. Regional silencing by the chimeras required Sir3 and Sir4, whereas gene-specific repression required Rfm1 and Sum1. Our findings demonstrate that the nonconserved N-terminal region and two amino acids within the enzymatic core domain account for cofactor specificity and proper targeting of these proteins. These results suggest that the differences in the silencing and repression functions of Sir2 and Hst1 may not be due to differences in enzymatic activities of the proteins but rather may be the result of distinct cofactor specificities.

* Corresponding author. Mailing address: Waksman Institute, 190 Frelinghuysen Rd., Piscataway, NJ 08854-8020. Phone: (732) 445-2905. Fax: (732) 445-5735. E-mail: vershon{at}waksman.rutgers.edu.

{triangledown} Published ahead of print on 22 January 2007.

{dagger} Present address: Department of Medicine, Stanford University, Palo Alto, CA 94305.

{ddagger} Present address: Genentech, South San Francisco, CA 94080.

Molecular and Cellular Biology, April 2007, p. 2466-2475, Vol. 27, No. 7
0270-7306/07/$08.00+0     doi:10.1128/MCB.01641-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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