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New Class of DNA Sequences Expands The Possibilities Of 'Reprogramming' Adult Cells Into Embryonic Ones
Discovery may aid effort to develop drugs, stem cell therapies to treat diseases
Feb 20, 2008 3:00 PM
University of Utah School of Medicine researchers have discovered a new class of gene-regulatory DNA sequences, a finding that has significant implications for changing adult cells into embryonic stem cells (ES cells) to research and potentially treat disease.
The discovery, published online in the journal Genome Research, may give researchers more control over regulating the process through which adult cells are changed or “reprogrammed” into ES cells, according to Dean Tantin, Ph.D., the study’s lead author and assistant professor of pathology. “This will affect our ability to understand and potentially control stem cell biology,” Tantin said. “It expands the number of DNA sequences we can target for reprogramming adult cells.”
Embryonic stem cells are highly valuable to researchers and physicians searching for ways to treat genetic-based diseases because they are pluripotent, meaning they can give rise to almost any cell in the human body. ES cells might, for example, be used to regenerate healthy cells in a heart damaged by congenital disease. Drugs might also be developed to target the genes that regulate ES cell development.
The ability to reprogram adult cells into ES cells generates an expanded base of these valuable cells. Four proteins help manage cell reprogramming. Tantin and colleagues in his lab were investigating one of these proteins, Oct4, when they discovered the new DNA sequences in the mouse and human genome.
Oct4 binds with DNA sequences to initiate the transfer of genetic instructions to reprogram adult cells. Prior studies of Oct4 had been from a “10,000-foot level,” but Tantin wanted to take a much closer look to understand how Oct4 binds with DNA. “We wanted to know how Oct4 does what it does,” he said. “During our research, we discovered new Oct4-binding sequences with unique biology.”
DNA is comprised of four compounds represented by pairs of letters (base pairs) strung together in long sequences. Theses sequences contain the genetic instructions for cell development. Tantin started by looking at many pieces of DNA, some with up to 2,000 base pairs. Then he isolated short sequences that bind with Oct4. To his surprise, he found a group of sequences unlike others that bind with the protein.
Oct4 typically binds in a single molecule with DNA sequences that have eight base pairs. But the new ones he identified have 15 to 20 base pairs and bind with two or more Oct4 molecules. These DNA sequences also respond to different molecular signals to bind with Oct4.
Because these new sequences are more complex, they come in many variations and Tantin now is studying the molecular mechanisms that bind them with Oct4. That mechanistic insight is essential for scientific advancement.
“We need to have a molecular understanding of what Oct4 is really doing before applying it to medicine or pharmacy,” Tantin said.
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|Dean Tantin, Ph.D.|
Department of Pathology
Phone: (801) 587-3035|
Office of Public Affairs
Phone: (801) 581-2517|
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