Abstract

Several different types of DNA elements in eukaryotic nuclei cause regional negative regulation of gene transcription, known as """"""""silencing."""""""" Among the best studied examples of silencing occur near telomeres and silent mating type loci in the budding yeast, Saccharomyces cerevisiae, but many additional examples of silencers have been identified in metazoans. This lab previously noted a third form of silencing in yeast. Transcription by RNA polymerase II is antagonized both upstream and downstream of tRNA genes. This inhibition, termed """"""""tRNA gene-mediated (tgm) silencing,"""""""" requires active transcription of the tRNA gene and does not arise from direct steric occlusion of nearby transcription factor binding. The extent of tgm silencing and the conditions under which it occurs are variable, depending on the pol II promoter. This ability of some pol ll promoters to selectively overcome the silencing effects suggest that tgm silencing is fundamentally different from other forms of silencing in yeast, and that it serves a regulatory function in at least some cases. These effects could influence a large number of loci, since large numbers of tRNA-class promoters are dispersed in throughout the genomes of most eukaryotes.
The aims of this project are to investigate the mechanism of conditional tgm silencing in yeast.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063142-03
Application #
6636655
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Carter, Anthony D
Project Start
2001-05-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
3
Fiscal Year
2003
Total Cost
$290,652
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Smaldino, P J; Read, D F; Pratt-Hyatt, M et al. (2015) The cytoplasmic and nuclear populations of the eukaryote tRNA-isopentenyl transferase have distinct functions with implications in human cancer. Gene 556:13-8
Pratt-Hyatt, Matthew; Pai, Dave A; Haeusler, Rebecca A et al. (2013) Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing. Proc Natl Acad Sci U S A 110:E3081-9
Moir, Robyn D; Lee, JaeHoon; Haeusler, Rebecca A et al. (2006) Protein kinase A regulates RNA polymerase III transcription through the nuclear localization of Maf1. Proc Natl Acad Sci U S A 103:15044-9
Haeusler, Rebecca A; Engelke, David R (2006) Spatial organization of transcription by RNA polymerase III. Nucleic Acids Res 34:4826-36
Wang, Li; Haeusler, Rebecca A; Good, Paul D et al. (2005) Silencing near tRNA genes requires nucleolar localization. J Biol Chem 280:8637-9
Thompson, Martin; Haeusler, Rebecca A; Good, Paul D et al. (2003) Nucleolar clustering of dispersed tRNA genes. Science 302:1399-401