Hidroximetilcitosina: uma base intrigante

segunda-feira, outubro 12, 2009

The Scientist

Volume 23 | Issue 10 | Page 21

By Jef Akst

Postdoctoral researcher Skirmantas Kriaucionis sat at the computer in the lab of molecular biologist Nathaniel Heintz at the Rockefeller University in New York, looking at an unidentified spot that hung mysteriously on the screen in front of him. He had been watching as, line by line, the scanned image of separated neuronal nucleotides took shape. Fifteen minutes later, the image was complete, but the picture was less clear than ever.

He immediately started repeating the experiment, reproducing the same result until he had convinced himself that the spot was real, and not just a mistake or an artifact of botched methodology. When Heintz came by his bench to see how the experiment was progressing, Kriaucionis showed him the unexpected results (Science, 324: 929–30, 2009).


Images of GFP-labeled Purkinje cell nuclei (left) and the chromatography results of the DNA nucleotides. The pencil points out the mysterious presence of hmC.
Courtesy of Skirmantas Kriaucionis

“As soon as I saw the spot, I thought it was important and interesting, [but] I didn’t believe it,” Heintz says. “[It] wasn’t A, G, C, or T, or methyl C”—the methylated form of cytosine (5-methylcytosine, or 5mC) and the only known modified base in mammalian DNA—“[so] we immediately knew there must be some other modified nucleotide in the genome of these neurons.”

The neurons in question were Purkinje cells, some of the largest neurons in the mammalian brain. Like some other large nerve cells, these cells contain giant nuclei—five to 10 times larger than the average nucleus—that have very little heterochromatin, the more tightly packed form of DNA. Curious about the reason for this peculiar structure, Kriaucionis and Heintz isolated these nuclei, as well as the nuclei of the smaller, heterochromatic granule cells for comparison, to quantify the amount of DNA methylation, which is associated with DNA packing. As suspected, they found less 5mC in Purkinje cells than granule cells, but surprisingly, no compensating increase in normal, unmethylated C. Instead, it appeared that a sixth nucleotide was taking up the slack.

Another series of tests revealed the mystery nucleotide’s identity as 5-hydroxymethylcytosine (hmC), a modified 5mC that had previously been identified in bacteriophages, but never conclusively in mammals. “It’s very exciting,” says molecular biologist Timothy Bestor of Columbia University, who was not involved in the work. “For the last 60 years we thought there was only one modified base in mammalian DNA. Now we know there’s at least two”—both of which are modified cytosines.

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NOTA IMPERTINENTE DESTE BLOGGER:

Espera-se que Kriaucionis não venha ter dificuldades com a Nomenklatura científica por nome de família meio esdrúxulo...

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NOTA DESTE BLOGGER:

Uma das predições da teoria do Design Inteligente é que, quanto mais acessarmos o DNA em níveis nunca dantes pesquisados, nós encontraremos cada vez mais o armazenamento de informação complexa especificada.

E ainda dizem que a TDI impede o avanço da ciência...