Epigenetic regulation of meiotic genes by the transcription factor Hac1i
A self-funded PhD studentship to investigate how the transcription factor Hac1i achieves epigenetic regulation of early meiotic genes is available in the group of Dr. Martin Schröder in the Department of Biosciences at Durham University, Durham, United Kingdom.
Unicellular organisms, such as the yeast Saccharomyces cerevisiae, are constantly exposed to several environmental stresses, such as heat, osmotic, or oxidative stress. In S. cerevisiae a general stress response provides protection against these diverse environmental stresses. Cells can also experience intracellular stress, for example endoplasmic reticulum (ER) stress, which is caused by the accumulation of mis- or unfolded proteins in the ER. This studentship will investigate how the ER stress signal is integrated into the general stress response.
In S. 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 Rpd3-Sin3 histone deacetylase (HDAC) through less understood mechanisms (1; 2). This studentship will specifically address the question how Hac1i modulates the subunit composition of the Rpd3-Sin3 HDAC to enhance transcriptional repression by this HDAC.
The student will map changes in the subunit composition of the Rpd3-Sin3 HDAC induced by Hac1i by using proximity biotin ligation assays with TurboID and then investigate whether these changes are necessary and sufficient for Hac1i to control HDAC activity. The student will be trained in cloning techniques, state-of-the-art molecular genetic techniques, co-immunoprecipitation techniques to characterise subunit incorporation into the Rpd3-Sin3 HDAC, and biochemical techniques to purify biotinylated proteins and identify these proteins by mass spectrometry.
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).
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].
1. Schröder M, Chang JS, Kaufman RJ: The unfolded protein response represses nitrogen-starvation induced developmental differentiation in yeast. Genes Dev 2000;14:2962-2975
2. Schröder M, Clark R, Liu CY, Kaufman RJ: The unfolded protein response represses differentiation through the RPD3-SIN3 histone deacetylase. EMBO J 2004;23:2281-2292