Cells Use Mix-and-match Approach To Tailor Regulation Of Genes

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Cells Use Mix-and-match Approach To Tailor Regulation Of Genes

http://www.medicalnewstoday.com/medicalnews.php?newsid=45419

Scientists eager to help develop a new generation of pharmaceuticals

are studying cellular proteins called transcription factors, which

bind to upstream sequences of genes to turn the expression of those

genes on or off. Some pharmaceutical companies are also hoping to

develop drugs that selectively block the binding of transcription

factors as a way to short-circuit the harmful effects of diseases,

and researchers at the University of California, San Diego on June 16

reported new findings that could aid that effort.

Bioengineering researchers at UCSD and two research institutes in

Germany report in the June 16 issue of PLoS Computational Biology

that transcription factors act not only in isolation, but also in

pairs, trios, and combinations of up to 13 to regulate distinct sets

of genes. The researchers, led by UCSD bioengineering professor Trey

Ideker, reported a list with 363 combinations of 91 central

transcription factors that regulate a large proportion of genes in

the yeast genome. The team used rigorous statistical tests to

discover active combinations of transcription factors, as if the

cells were mixing and matching parts of its regulatory-protein

wardrobe to respond to different environmental conditions. The

researchers expect that human cells use a similar system of

transcription-factor combinations, but on a larger scale.

" A cell's surprising ability to mix and match so many different

combinations of these factors to achieve a high degree of complexity

and specificity in the expression of its genes is impossible for even

the most experienced cell biologists to conceptualize, " said s

Beyer, a post-doctoral fellow at the UCSD s School of

Engineering's Department of Bioengineering. " That's why we have

computers. "

The researchers combined the results of their laboratory with other

large-scale measurements of transcription factor-gene binding, such

as those reported earlier by MIT biology professor A. Young

and his collaborators.

Ideker's team was able to identify new transcription factor binding

patterns by borrowing a concept from computer science. The team

considered the binding of one transcription factor to one gene as

analogous to one " hop " of a data packet from one Internet router to

another.

In the case of gene regulation, Ideker's team identified " 2hop "

relationships by first focusing on single transcription factor-gene

associations, plus other experimental evidence that indicates that

that gene regulates a second gene.

To enlarge the scope of the model further, Ideker's group also

incorporated other previously discovered transcription-factor

interactions and related genetic results. They relied on a total of

eight types of direct and indirect evidence to create a model. That

model predicts 980 as-yet-undiscovered transcription factor-gene

binding interactions.

" This 'systems biology' approach, using so many different lines of

evidence, has given us a much more revealing and detailed picture of

how cells orchestrate gene regulation to cope with different

environments, " said Ideker. " We're far from understanding the full

picture of gene regulation in a cell, but this new information should

give scientists who are interested in blocking transcription factors

a powerful new tool to narrow their search to the most promising

candidates. "