Regulation of the Rpd3L histone deacetylase by the transcription factor Hac1
A self-funded PhD studentship to investigate integration of several stress signals into transcriptional regulation by the Rpd3 histone deacetylase in Saccharomyces cerevisiae is available in the group of Dr. Martin Schröder in the School of Biological and Biomedical Sciences at Durham University.
The accumulation of mis- or unfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates a signalling network called the unfolded protein response (UPR). In the yeast Saccharomyces cerevisiae the transcription factor Hac1i transduces the ER stress signal and directly activates expression of many ER stress-responsive genes by binding to ER stress response elements in their promoters. Hac1i also controls transcriptional regulation of early meiotic genes by the large Rpd3-Sin3 histone deacetylase complex (Rpd3L) through less well understood mechanisms (1; 2). Rpd3L is known to deacetylate several acetylated lysines in the N-terminal tails of the histones to repress transcription initiation. The aim of this studentship is to characterise to which extent deacetylation of the histone tails by Rpd3L is required for Rpd3L-dependent repression of early meiotic genes by Hac1i.
The successful candidate will use molecular genetics to produce yeast strains in which the N-terminal tails of the histones have been deleted and in which lysines in the N-terminal tails have mutated. The effect of these mutations on repression of early meiotic genes by Hac1i will be studied in beta-galactosidase reporter assays, Northern blots, and quantitative reverse transcriptase PCR assays for early meiotic genes.
Applicants should possess at least a 2:1 Honours degree, or equivalent, in an appropriate subject (e.g. biochemistry, cell biology, molecular biology, or genetics) and bring a strong interest in molecular biology to the project.
If you are interested in applying, send your CV and covering letter detailing your reasons for applying for this studentship to the prospective project supervisor, Dr. Martin Schröder, at [email protected]