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Gene-transcription machinery seen poised for action, held in check until needed

(PHILADELPHIA) For some time, scientists have been tracking down the sequence of biochemical steps required to attract and assemble at the head end of a gene the molecular machinery needed to transcribe that gene to put to work the information it encodes. Now, a new study led by researchers at The Wistar Institute suggests that the gene-transcription machinery, once in place, can remain poised for action but held in check until a triggering signal sends it on its way down the linear DNA molecule.

The data outline a mechanism by which sets of critical genes could be prepared for nearly instantaneous activation in response to stress or other vital needs. Embryonic stem cells, for example, are known to have numbers of genes held in this state of readiness.

In their investigations, the scientists were able to identify a single molecule called ubiquitin that, when in place, appears to be able to pause the transcription process after the needed machinery has been assembled. Once that molecule is removed, the machinery with a molecule known as RNA polymerase II at its core is released and transcription is set into motion. The research was done in yeast, an often-used model organism for genetic studies. A report on the findings appears in the current issue of Molecular Cell.

In our experiments, we saw polymerase loaded onto the gene, but not correctly activated, says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. At the appropriate time, ubiquitin is removed, and this triggers polymerase action. Data from other laboratories indicate that stem cells have many genes that may be poised in this way, ready to send the cells down various differentiation pathways to form different tissues. There are likely many vital cell functions that depend on a quick response which could be regulated by this process.

In earlier work, Berger and her coworkers looked at ways in which
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
25-Jul-2007


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