While trying to understand the molecular underpinnings of a protein that helps turn adult cells into embryonic stem cells, University of Utah researchers found a new class of gene-regulating DNA sequences. They say this "incremental step" has significant implications for reprogramming adult cells to become stem cells to research and possibly treat disease one day.
"The better we understand how these proteins work, the more we will be able to control the process, with greater nuance. If we understand how (the protein) Oct4 works, we can get it to do what we want rather than a global process. The result could be superior medicines less of a blunt instrument, more of a finer point," says Dean Tantin, Ph.D., assistant professor of pathology and lead author of the study, published online in the journal Genome Research.
Researchers prize embryonic stem cells because they can become many different types of cells in the human body. Ongoing research worldwide gives hope that stem cells can be used to generate healthy cells to replace those that are damaged in congenital disease, for instance. Eventually, drugs may be developed to target the genes that regulate stem cell development.
Their research subject, Oct4, is one of four proteins that help manage that cell reprogramming. The protein, says Tantin, "binds" with DNA sequences to begin sending genetic instructions to reprogram adult cells. They were hoping to figure out how Oct4 binds with DNA; unexpectedly, they found new and very different binding sequences.
Four compounds that are represented by pairs of letters in long sequences make up DNA. The sequences are the manual for cell development. After looking at long strips of DNA, Tantin isolated smaller sequences that bind with Oct4. He was surprised to find a group unlike the others, which have eight base pairs of letters and bind with a single Oct4 molecule. The new ones have up to 20 base pairs and bind with two or more of the protein molecules.
"It acts differently, reacts to different signals and binds in a different way," Tantin says, adding that once they understand the process, it should lead to medicines and pharmaceutics.
Oct4 is only expressed in stem cells and a restricted set of cells, so it's interesting from a therapeutic viewpoint, but doesn't necessarily lead to understanding of other cells. Another high-interest protein, Oct1, is expressed everywhere. Since the two proteins look like each other and bind and are regulated the same way, their research into Oct4 will inform their study of Oct1 and vice versa, he says.The discovery of the new sequence biology opens the door to important research. "The implications are big," Tantin says.