Cells face the challenge of storing two meters of DNA in the three-dimensional 
(3D) space of the nucleus that spans only a few microns. The nuclear 
organization that is required to overcome this challenge must allow for the 
accessibility of the gene regulatory machinery to the DNA and, in the case of 
embryonic stem cells (ESCs), for the transcriptional and epigenetic changes that 
accompany differentiation. Recent technological advances have allowed for the 
mapping of genome organization at an unprecedented resolution and scale. These 
breakthroughs have led to a deluge of new data, and a sophisticated 
understanding of the relationship between gene regulation and 3D genome 
organization is beginning to form. In this review we summarize some of the 
recent findings illuminating the 3D structure of the eukaryotic genome, as well 
as the relationship between genome topology and function from the level of whole 
chromosomes to enhancer-promoter loops with a focus on features affecting genome 
organization in ESCs and changes in nuclear organization during differentiation.