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Date:2/4/2013

it is largely associated with DNA that is loosely looped about its protein scaffolding in the nucleus. The 5mC signal, meanwhile, is predominantly located on more tightly packed, less accessible stretches of DNA. It is on the loosely packed DNA that most gene expression takes place.

In line with that finding, they discovered that the 5hmC marker was scattered over regions of the genome where genes are being expressed at high levels. And in concurrence with other studies, they found that the 5mC signal was mainly located on silent islands of the genome.

When the researchers peered more closely at the DNA sequence, they further discovered that 5hmC is largely planted within gene bodiesthe parts of genes that encode proteinsnot in intervening sequences that mark where the coding regions begin (promoters) and determine how avidly the genes are expressed (enhancers). This surprised them, as it is in such sequences that one would expect an on switch for a gene to be located. "It's easy to see how a modification of enhancer or promoter regions might affect gene expression," says Kriaucionis, PhD, and an assistant member of the Ludwig Institute at Oxford University.

"Indeed, we know 5hmC is found in those sequences in embryonic stem cells, which give rise to the whole body. But it is much less clear how the placement of this marker on the gene bodywhich contains the instructions for making a protein, not the sequences that determine when or how much of it is madecould have such a pronounced effect on gene activation."

Kriaucionis and colleagues in Nathaniel Heintz' team also discovered that in places where 5hmC is common, 5mC is found at low levels, and vice versa. Further, the patterns and ratios of the two markers and the genes highly expressed in each of the cells assessed varied dramatically. This implies that preexisting molecular signals that are unique to each kind of cell are vital to determining where exactly the 5hmC mark
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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