Whitehead Institute researchers have created a map of the DNA loops that comprise the three dimensional (3D) structure of the human genome and regulate gene expression in human embryonic stem (ES) cells and adult cells. The location of genes and regulatory elements within this chromosomal framework could help scientists better navigate their genomic research, establishing relationships between mutations and disease development.
“This is transformational,” says Whitehead Member Richard Young. “This map allows us to predict how genes are regulated in normal cells, and how they are misregulated in disease, with far greater accuracy than before.”
In order to regulate gene expression
, a regulatory element needs to contact its target gene. Through looping, element/gene partners that are distant from each other in linear DNA can be brought together. Most disease mutations occur in regulatory elements, but if the partnership between a seemingly far-flung gene and the regulatory element is not known, the mutation data is of limited use. This draft map, which can help scientists predict the relationships between mutated elements and their target genes, is described online this week in the journal Cell Stem Cell.
“When thinking about disease, we need to think about the structure of the genome in 3D space because that is how we now understand that genes are regulated,” says Xiong Ji, a postdoctoral researcher in the Young lab and a co-author of the Cell Stem Cell paper.