Shining a light on gene regulation

The human genome is not randomly organised in the cell nucleus. Some sequences are preferentially found at the nuclear periphery, others in the nuclear interior. Some genome regions are packaged more tightly than others and chromosome folding can spatially juxtapose sequences that are far apart on the linear DNA. Therefore beyond the human DNA sequence and epigenetic maps of chromatin modifications, there needs to be an investigation of 3D genome organisation in order to understand how the genome is regulated in development and disease.
I will discuss the important role of high-resolution sub-cellular imaging in investigating the spatial organisation of the mammalian genome and I will describe how this can be coupled with synthetic epigenome editing tools to determine the structure/function relationships between the genome organisation, chromatin structure, transcription and DNA replication. I will also show how an analysis of 3D chromosome folding is contributing to an understanding of how cis-acting regulatory sequences can act on their target genes located up to a million bases away.