Unique and shared roles of subunits of the Drosophila tMAC transcriptional regulation complex
Applicants (UK, EU and international) capable of self-funding or with scholarship are welcome to apply.
Differential gene expression underlies the tissue- and developmental stage-specific differences between cells in multi-cellular organisms. Transcriptional regulation ensures the appropriate genes are switched ON or OFF in any specific cell. A conserved multi-subunit complex (LINC), is responsible for regulating transcriptional activity of many different target genes. The Drosophila LINC-related complex, tMAC, controls expression of at least 2000 genes in the male germline, and is essential for normal sperm production. tMAC contains at least 4 predicted DNA binding proteins, all of which need to be present for the complex to function, despite the fact that their target promoters can be very short. Intuitively one would expect all the core subunits of this complex to work together to regulate the same target genes, however, via mutation of individual core complex subunits, we have revealed that they have unique as well as shared roles. Intriguingly we have found that some complex components switch from being repressive to being activatory depending on the presence of other subunits.
The project will aim to answer the following questions:
What are the unique and shared roles of tMAC core components?
How do specific subunits activate gene expression from some promoters while acting as silent partners, or even repressors at other promoters?
Why are four different DNA binding proteins present in the complex? Do they all bind directly to the target promoters?
Are all the complex subunits present at all target promoters, or are there specific sub-complexes with defined functions?
In answering these questions you will gain skills in advanced Drosophila genetics, cell biology and biochemistry methods coupled with molecular biology techniques including ChIP-Chip (or ChIP-seq), microarray analysis and bioinformatics.
WHITE-COOPER, H. 2010. Molecular mechanisms of gene regulation during Drosophila spermatogenesis. Reproduction, 139, 11-21.