On July 21, 2011, researchers with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA announced a breakthrough in stem cell research. They have generated the first genome-wide mapping of a DNA modification called 5-hydroxymethylcytosine (5hmC) in embryonic stem cells, and discovered that it is predominantly found in genes that are turned on, or active. This development may prove to be important in controlling diseases such as cancer, where the regulation of certain genes plays a role in disease development. The molecule 5hmC was only recently discovered, and its function has not been clearly understood, said Steven E. Jacobsen, a professor of molecular, cell and developmental biology in the Life Sciences and a Howard Hughes Medical Institute investigator. He added that, until now, researchers did not know where 5hmC was located within the genome. “That is important to know because it helps you to understand how it is functioning and what it’s being used for,” said Jacobsen, who also is a researcher with UCLA’s Jonsson Comprehensive Cancer Center. “We had known that DNA could be modified by 5hmC, but it wasn’t clear where on the genome this was occurring.”
Jacobsen, whose lab studies the molecular genetics and genomics of DNA methylation patterning, used genomics to define where in human embryonic stem cells the 5hmC was present. They used human embryonic stem cells because it had been shown previously that the molecule is abundant in those cells, as well as in brain cells, Jacobsen said. In the study, Jacobsen found that 5hmC was associated with genes and tended to be found on genes that were active. The study also revealed that 5hmC was present on a type of DNA regulatory element, called enhancers, which help control gene expression. In particular, 5hmC was present on enhancers that are crucial for defining the nature of the human embryonic stem cells.
“If we can understand the function of 5hmC, that will lead to greater understanding of how genes are turned on and off and that could lead to the development of methods for controlling gene regulation,” Jacobsen said. Moving forward, Jacobsen and his team will seek to uncover the mechanism by which 5hmC is created from DNA methylation and how it becomes localized to particular areas of the genome, such as the enhancers.
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