Selective control of tRNA gene transcription by steroid receptors and BRCA1

BRCA1 is an important tumour suppressor protein with roles in DNA repair
and transcription. BRCA1 binds many tRNA genes, but its role there is
unknown. This project will test if repression of tRNA gene transcription by
BRCA1 is part of its function as a tumour suppressor.
Oestrogen drives proliferation of breast cells and its receptor is targeted by
the widely-used drug tamoxifen. Oestrogen receptor binds and activates
tRNA genes, effects that are countered by tamoxifen. Progesterone can also
antagonize the mitogenic effects of oestrogen. The progesterone receptor
was recently found to interact with RNA polymerase III at specific tRNA
genes and repress their expression. We will investigate how oestrogen and
progesterone receptors select tRNA genes and influence transcription at
these sites.
This project will provide extensive training in molecular interactions between
key genes and factors with massive impact on cell biology and human health.