Using high-throughput methods to study the regulatory grammar in neurons
One of the most important methods for regulating gene expression is through transcription factor (TF) binding. Today, there are powerful methods, such as ChIP-seq, that allow us to identify where a TF will bind in vivo. These methods, however, do not provide any information about how a binding event affects downstream gene expression. To study the impact of different TF binding motifs, we have developed the Massively Parallel Reporter Assay (MPRA) (Melnikov et al, Nature Biotech, 2012) and applied it to neurons. Our goal was to investigate activity dependent gene expression, a programme central to memory and learning. I will describe how we were able to identify and validate regulatory motifs that had not been previously implicated in activity-dependent gene expression. I will also discuss our efforts to identify the regulatory grammar - i.e. the rules for how combinations of motifs determine gene expression.
Martin's research interests are overlapping with many of ours, as nicely summarised by the title of one of his recent papers:
"Tau promotes neurodegeneration through global chromatin relaxation"