Organization and Regulation of the Human Genome

The 3-dimensional (3D) chromatin organization plays a critical role in gene regulation. Great strides have been made recently to characterize and identify cis regulatory elements from epigenome profiles in different cell types and tissues, but efforts have just begun to functionally characterize these long-range control elements. Mapping interactions between enhancers and promoters, and understanding how the 3D landscape of the genome constrains such interactions is fundamental to our understanding of genome function. I will present recent findings related to 3D genome organization in mammalian cells, with a particular focus on how chromatin organization contributes to transcriptional regulation. I will describe higher-order organizational features that are observed at the level of both the whole chromosome and individual loci. I will highlight changes in genome organization that occur during the course of differentiation, and discuss the functional relationship between chromatin architecture and gene regulation. Taken together, mounting evidence now shows that the genome organization plays an essential role in orchestrating the lineage-specific gene expression programs through modulating long- range interactions between enhancers and target genes.