CArG boxes exert their influence over genes because they are "shaped" to partner with a nuclear factor called serum response factor (SRF) and several other proteins within a genetic regulatory network. Throughout a human life, such networks are believed to "decide" the timing and location of all gene expression, the process through which genetic information is converted into templates for protein construction.
The current study, funded through a grant from the National Heart, Lung and Blood Institute, sought to survey the human and mouse genome databases created by the Human Genome Project to find all CArG boxes that regulate genes. The sheer amount of information involved requires that such studies use high-powered computer programs to screen data. In this case, researchers used a high-speed screening to expand the definition of the functional mammalian CarGome, the complete set of CArG boxes that regulate genes.
In collaboration with Christian Stoeckert, Ph.D., associate professor of Genetics at the University of Pennsylvania, Miano's team designed a set of criteria that a given piece of DNA had to meet in order to be considered a functional CArG box. Thanks to their work and that of several other labs, they knew going in all the CArG box variations and how close they typically lie to the genes they regulate (within 4,000 base pairs).
The data-screening tool also employed comparative genomics, the study of relationships between the DNA of different species. When a piece of genetic material, gene or regulatory segment, is conserved by evolution from mice to humans it suggests that the segment has a valuable function. Miano's screen required that CArG boxes shared by humans and mice be included in his expanded version of the CarGome. CArG boxes identified by the computer screen were then tested to see if they indeed interacted with SRF and changed the behavior of genes as pred
Source:University of Rochester Medical Center