Dynamic interplay of the SUMO and MAP kinase pathways; role of transcriptional integrators in regulating transcriptome readout. (360G-Wellcome-078085_Z_05_Z)

The establishment and subsequent control of specific gene expression programmes in response to extracellular signals, is one of the central processes governing cellular function and identity. The overall aim of our programme is to understand how specific outcomes to signalling pathways are achieved. To do this, we will focuss on studying how responses to MAPK signaling are elicited through differential gene regulation via specific transcription factor-coactivator complexes. To achieve this, we will;· Probe how two novel coactivator/integrator proteins PIASxa and LPP control the activity of ETS-domain transcription factors Elk-1 and PEA3 respectively. · Determine the role of these coactivators in regulating gene expression in a broader context.· Determine how the MAPK and SUMO pathways interact to control the output of MAPK signalling through these complexes.To achieve these aims, we will make extensive use of modern promoter microarray and RNAi-based screening technologies, coupled with bioinformatic techniques to provide an integrated genomics approach to our work. Importantly though, our work will incorporate detailed molecular analysis to complement the genomics-based studies, permitting iterative rounds of hypothesis generation and testing.