Our group is interested in understanding the interplay between gene regulation and genome architecture, towards defining rules and principles of genome function.
We study mechanisms of gene expression at multiple levels, from the local action of transcription factors, to long-range chromatin looping events that connect regulatory DNA sequences with the genes they regulate, to how whole chromosomes are positioned within cell nuclei. Binding of transcription factors at gene promoters helps recruit chromatin remodelers and the transcription machinery to transcription sites. Upon recruitment, RNA polymerases either remain primed for subsequent activation (e.g. after environmental stress, during differentiation or disease), or directly transcribe the DNA template into RNA molecules, which code for proteins or for structural RNAs that constitute many enzymatic complexes. An increasingly important aspect of gene regulation are the mechanisms by which distant regulatory DNA sequences physically interact with gene promoters to recruit or activate RNA polymerase II (RNAPII), the enzyme responsible for transcribing protein-coding genes, and many structural and regulatory RNAs.
Our long-term strategy for unravelling the principles of genome function in higher eukaryotes aims to integrate multiple parameters, which is becoming increasingly possible with state-of-the-art developments in molecular biology, epigenetics, nuclear imaging, proteomics and genetics.