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Charting the epigenome
Date:4/17/2008

n since we still have a very poor understanding of the genome-wide regulation of methylation and its effect on the transcriptome, explains postdoctoral researcher and co-first author Ryan Lister, Ph.D.

The transcriptome encompasses all RNA copies or transcripts made from DNA. The bulk of transcripts consists of messenger RNAs, or mRNAs, that serve as templates for the manufacture of proteins but also includes regulatory small RNAs, or smRNAs. The latter wield their power over gene expression by literally cutting short the lives of mRNAs or tagging specific sequences in the genome for methylation.

But before Lister could start to unravel the multiple layers of epigenetic regulation that control gene expression, he had to pioneer new technologies that allowed him to look at genome-wide methylation at single-base resolution and to sequence the complete transcriptome within a reasonable timeframe.

Collaborating scientists at the ARC Centre of Excellence in Plant Energy Biology at the University of Western Australia in Perth developed a powerful, web-based genome browser, which played a crucial role in unlocking the information hidden in the massive datasets.

Cells employ a whole army of enzymes that add methyl groups at specific sites, maintain established patterns or remove undesirable methyl groups. When Lister and his colleagues compared normal cells with cells lacking different combination of enzymes they discovered that cells put a lot of effort in keeping certain areas of the genome methylation-free.

On the flipside, the Salk researchers found that when they knocked out a whole class of methylases, a different type of methylase would step into the breach for the missing ones. This finding is relevant for a new class of cancer drugs that work by changing the methylation pattern in tumor cells.

You might succeed in removing one type of methylation but end up with increasing a different type, says Ecker. But ve
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Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute
Source:Eurekalert

Page: 1 2 3

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1. $10 million gift to support cutting-edge epigenome center at USC
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