Researchers create atlas of transcription factor combinations

March 4, 2010

In a significant leap forward in the understanding of how specific types of tissue are determined to develop in mammals, an international team of scientists has succeeded in mapping the entire network of DNA-binding transcription factors and their interactions. This global network, indicating which factors can combine to determine cell fate, will be published in the March 5 issue of the journal Cell.

Transcription factors (TFs) are proteins that bind to specific in order to direct which genes should be turned on or off in a tissue. Tissue specificity - whether embryonic tissue develops into lungs or kidneys or skin, for example - is determined by how and which TFs bind to genes. Between 2,000 and 3,000 transcription factor proteins are encoded by the human , potentially creating more than 4 million potential protein pairings.

It has long been appreciated that different combinations of TFs are active in different tissues. But given the enormous number of TFs and potential pairings, it has been difficult to precisely identify which combinations are functional, according to principal investigator Trey Ideker, PhD, chief of the Division of Genetics at the University of California, San Diego, School of Medicine.

The integrated approach to systematically map all possible combinations of TFs in has generated large data sets in both humans and mice. The complete network contains 762 human and 877 mouse interactions between TFs, indicating TF pairs that can work in combination.

"The availability of this large combinatorial network of will provide scientists with many opportunities to study , tissue differentiation and evolution in mammals," said Ideker, professor in the Department of Medicine and at UCSD's Jacobs School of Engineering. He added that analysis of the network shows that highly connected TFs are broadly expressed across tissues, and that roughly half of the interactions are conserved between mouse and human.

The researcher team identified nearly 1,000 different pairs of TF proteins that can be wired together, representing the blueprint of all possible combinations that direct gene expression in mammals. The work may provide researchers with the clues necessary to one day determine how stem cells can be reprogrammed into a particular organ or tissue type.

The research team comprised 41 scientists from 17 different institutions around the world.

Explore further: Putting microRNAs on the stem cell map

Related Stories

Putting microRNAs on the stem cell map

August 7, 2008

Embryonic stem cells are always facing a choice—either to self-renew or begin morphing into another type of cell altogether. It's a tricky choice, governed by complex gene regulatory circuitry driven by a handful of key ...

Scientist explores secrets to life through worms

October 17, 2008

Who would have thought that worms found in your composter - only seen with a microscope - could be used to study genetic disorders in humans? With 700 million years of separation and roughly half of its genes similar to humans, ...

How cells change gears

April 20, 2009

Bioinformatics researchers from UC San Diego just moved closer to unlocking the mystery of how human cells switch from "proliferation mode" to "specialization mode." This computational biology work from the Jacobs School ...

'Moonlighting' molecules discovered

October 29, 2009

Since the completion of the human genome sequence, a question has baffled researchers studying gene control: How is it that humans, being far more complex than the lowly yeast, do not proportionally contain in our genome ...

Recommended for you

Secrets of a heat-loving microbe unlocked

September 4, 2015

Scientists studying how a heat-loving microbe transfers its DNA from one generation to the next say it could further our understanding of an extraordinary superbug.

Plants also suffer from stress

September 4, 2015

High salt in soil dramatically stresses plant biology and reduces the growth and yield of crops. Now researchers have found specific proteins that allow plants to grow better under salt stress, and may help breed future generations ...

Ancient walnut forests linked to languages, trade routes

September 4, 2015

If Persian walnut trees could talk, they might tell of the numerous traders who moved along the Silk Roads' thousands of miles over thousands of years, carrying among their valuable merchandise the seeds that would turn into ...

Huddling rats behave as a 'super-organism'

September 3, 2015

Rodents huddle together when it is cold, they separate when it is warm, and at moderate temperatures they cycle between the warm center and the cold edges of the group. In a new study published in PLOS Computational Biology, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.