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.
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 in the journal Cell Stem Cell.
To devise this map, authors identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states.
Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions they identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation
These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.
http://wi.mit.edu/news/archive/2015/3d-map-human-genome-reveals-relationship-between-mutations-and-disease-development
Edited
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