Humans have "at least" four million on-off switches to control 21,000 genes!

Gina Kolata writes in the New York Times about the discovery that “the human genome is packed with at least 4 million on-off switches that tell our genes what to do and when. The switches reside in bits of DNA that once were dismissed as “junk” but turn out to play critical roles in controlling how cells, organs and other tissues behave.”

“As they delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered it is not junk. At least 80 percent of it is active and needed.
The result is an annotated road map of much of this DNA, noting what it is doing and how. It includes the system of switches that, acting like dimmer switches for lights, control which genes are used in a cell and when they are used, and determine, for instance, whether a cell becomes a liver cell or a neuron.”
 
“The findings have applications for understanding how alterations in the non-gene parts of DNA contribute to disease, which might lead to new drugs.
They can also help explain how the environment can affect disease risk. In the case of identical twins, small changes in environmental exposure can slightly alter gene switches, with the result that one twin gets a disease and the other does not.”
 
“In one of the Nature papers, researchers link the gene switches to a range of human diseases — multiple sclerosis, lupus, rheumatoid arthritis, Crohn’s disease, celiac disease — and even to traits like height.
In large studies over the past decade, scientists found that minor changes in human DNA sequences increase the risk that a person will get those diseases. But those changes were in the junk, now often referred to as the dark matter — they were not changes in genes — and it was not clear what their significance was. The new analysis reveals that a great many of those changes alter gene switches and are highly significant.
“Most of the changes that affect disease don’t lie in the genes themselves; they lie in the switches,” said Michael Snyder, a Stanford University researcher for the project, called ENCODE, for Encyclopedia of DNA Elements.”

“Why would you need to have a million switches to control 21,000 genes?”
There also is a sort of DNA wiring system that is almost inconceivably intricate.”