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Updated: Jul 30, 2026

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Targeted in Situ Mutagenesis of Histone Genes in Budding Yeast
Published on: January 26, 2017
Genomewide studies of histone deacetylase function in yeast
B E Bernstein1, J K Tong, S L Schreiber
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology and Center for Genomics Research, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Summary
Yeast histone deacetylase (HDAC) Rpd3p has dual roles, repressing and activating transcription. Rpd3p regulates genes involved in cell cycle, biosynthesis, and transport, impacting telomeric gene silencing.
Area of Science:
- Molecular Biology
- Epigenetics
- Yeast Genetics
Background:
- Histone deacetylases (HDACs) regulate gene expression.
- Trichostatin A (TSA)-sensitive Rpd3p and TSA-resistant Sir2p are key yeast HDACs.
- Rpd3p functions in a complex with Sin3p and Sap30p, recruited by factors like Ume6p.
Purpose of the Study:
- To investigate the transcriptional roles of yeast HDACs, particularly Rpd3p.
- To elucidate the mechanisms by which Rpd3p regulates gene expression, including telomeric silencing.
- To identify feedback loops modulating HDAC activity.
Main Methods:
- Transcriptional profiling of yeast strains with deletions or TSA treatment.
- Bioinformatic analysis of gene promoters and regulatory elements.
- Analysis of gene expression changes near telomeres.
Main Results:
- Rpd3p deletion shows transcriptional profiles similar to sin3, sap30, ume6, and TSA-treated yeast.
- Rpd3p represses ZRT1 (zinc transporter) and BNA1 (NAD biosynthesis) via feedback loops.
- Rpd3p deletion down-regulates 40% of endogenous genes near telomeres, suggesting roles in histone regulation and SIR-mediated silencing.
Conclusions:
- Rpd3p exhibits both transcriptional repression and activation functions.
- Rpd3p plays a critical role in regulating telomeric gene silencing, potentially through histone modification.
- Distinct yeast HDACs (Rpd3p, Sir2p, Hda1p) have specialized roles in regulating diverse cellular processes.
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