Transcription factor chorus

July 14, 2000

Reading the genome is nothing new - nature has been doing it for billions of years.

If only we knew how. Robert Tjian, a biochemist at the University of California, Berkeley, has been grappling with understanding this by studying the actual machinery that does the task.

"The process is mind-bogglingly complex and uses very sophisticated, fantastically elegant machinery," Dr Tjian says.

"There are perhaps 100,000 genes in the human genome, each with a very specific time and place for it to be read and activated."

About 100 different proteins, collectively known as transcription factors, have to work together in a highly coordinated fashion to read a particular gene.

The process begins with sequence specific, DNA-binding proteins that can browse the genome to find their target.

They then manoeuvre themselves to the appropriate spot around the gene and act as a magnet to attract the next set of chemicals.

These proteins in effect instruct how the gene should be read.

Finally, the proteins that form transcription machinery itself, which assembles messenger RNA to match the DNA of the gene, fit on top of this vast complex of chemicals.

At this point, the gene is functional -the RNA that gets churned out heads off to create the specific protein that the gene codes for and the rest is biochemical history.

"The collective interpretation of these different molecules makes the overall machinery very smart," Dr Tjian says.

The crucial details of this process are slowly surfacing from the emerging field of proteomics, the analysis of the proteins that the genetic code describes.

Perhaps as many as 10,000 genes are involved and it seems that different cell types use machinery made from different proteins.

Yet there is a strong incentive to tackle the complexity - if drugs could be designed to selectively intervene in this process, a very powerful new way to tackle disease would open up.

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