Stem cell researchers at UCLA 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.
The finding by researchers with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA may prove to be important in controlling diseases like cancer, where the regulation of certain genes plays a role in disease development.
"Any way you can control genes will be hugely important for human disease and cancer," said Steven E. Jacobsen, a professor of molecular, cell and developmental biology in the Life Sciences and a Howard Hughes Medical Institute investigator. "Cancer is generally a problem of genes being inappropriately turned off or mutated, like tumor suppressors genes, or genes that should be off getting switched on."
The study appears in the July issue of the journal Genome Biology.
5hmC is formed from the DNA base cytosine by adding a methyl group and then a hydroxy group. The molecule is important in epigenetics - the study of changes in gene expression caused by mechanisms other than changes in the DNA sequence - because the newly formed hydroxymethyl group on the cytosine can potentially switch a gene on and off, Jacobsen said.
The molecule 5hmC was only recently discovered, and its function has not been clearly understood, Jacobsen said. Until now, researchers didn't 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 methyla
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University of California - Los Angeles Health Sciences