This approach resulted in the disclosure of more than 100 hypothetical CArG boxes and the same number of genes previously unknown to be targeted by CArG-SRF. Of those, 60 CArG boxes have been validated as exerting influence over a gene. Adding the newly confirmed segments to those already known, authors of the study now define the functional mammalian CarGome as 161 sequences, a 55 percent increase from the old definition.
Of the genes newly found to be regulated by CArG-SRF, more than half encode for cytoskeletal or contractile proteins. Past studies have shown that CArG-SRF network is vital to the development of the cellular "skeletons" that maintain cell shape and enable cell motion. Being present in nearly every cell and throughout the human genome, the CArG-SRF system is believed to contribute to disease in many bodily tissues.
In cardiology, studies show that a lack of SRF-CArG causes cardiomyopathy, a weakening of heart muscle cells' ability to contract. That in turn reduces the pumping strength of heart muscle and leads to heart failure, according to recent studies. Can cardiomyopathy be reversed by manipulating CArG-SRF? CArG sequences also appear near genes that direct the building of nerve cells and blood vessels, suggesting they may be involved in diseases affecting those tissues as well.
In the larger picture, regulatory sequences may help to explain why humans have just 25,000 genes when, given the degree of human complexity, researchers had expected to find more than 100,000. Regulatory sequences may be part of the answer because they enable a single gene to produce the same protein at different times, places and concentrations with subtly different roles.
"Humans share about one quarter of their genes with fish," Miano said. "Something must be at work to explain why we are so many times more complex. Regulatory sequences offer one of several emerging explanations for how we do more with fewer ge
Source:University of Rochester Medical Center