Important find shows how gene regulators select different partners to form different organs

Mar 14, 2013

Scientists at the Agency for Science, Technology and Research's (A*STAR) Genome Institute of Singapore (GIS) have discovered that key gene regulators work in pairs to trigger stem cells to differentiate into specific cell types. Furthermore, they showed that selective partnering of the regulators result in uniquely specified developmental outcomes.

An embryo develops from a single cell to a complex, interconnected assemblage of multiple cell types in the adult organism, such as the muscles, nerves, lungs and heart. The fates of as they differentiate into specialized require tightly regulated expression of hundreds of genes; each cell type being regulated by a unique and specific pattern of . Transcription factors are master regulators of gene expression and have been implicated as key players in the appropriate specification embryo development. They do this by binding to DNA thereby "turning on" or "turning off" nearby genes. What is less clear is how these transcription factors select specific sets of genes for activation and repression.

A recent study by scientists from GIS has discovered that it takes a pair of transcription factors, working tightly together, to orchestrate key decisions in . The discovery was published in the prestigious EMBO Journal.

The study, a multidisciplinary collaborative effort, established that the transcription factor Oct4 alternatively partners with two related factors, Sox2 or Sox17. This paper, together with a related paper published in the journal Stem Cells in 2011 ("Conversion of Sox17 into a reprogramming factor by re-engineering its association with Oct4 on DNA."), makes a key discovery about how the selective partnering of the two can lead to very different .

Lead author Dr. Lawrence Stanton said, "This work was a unique collaboration between scientists hailing from different areas of expertise – , cell biology, developmental biology and biochemistry. The unique line of research was only possible by the interdisciplinary efforts of these scientists."

Co-lead author Dr. Prasanna Kolatkar said, "Our previous work described how re-engineering of developmental proteins through a single site change results in functions of proteins Sox2 and Sox17 becoming inter-converted – thus the decision to stay as a stem cell or differentiate is flipped through a single amino acid change. This study uses a genome-wide approach to validate this concept, and moreover leads to novel genes potentially involved in primitive endoderm formation."

"This work identified a novel regulatory switch from pluripotency to cell-lineage specific differentiation. It is remarkable that a single pluripotency factor, Oct4, was found to influence diverse cellular processes. This key discovery illustrates the complexity in the regulation of pluripotency programme in embryonic stem cells," said GIS Executive Director Prof Ng Huck Hui.

Explore further: Cold improves longevity for some C. elegans worms, shortens life span for others

More information: Aksoy, I. et al. Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm, The EMBO Journal, 8 March 2013.

Related Stories

Scientists discover switch to speed up stem cell production

May 18, 2011

A team of scientists from Genome Institute of Singapore (GIS) of the Agency for Science, Technology and Research (A*STAR) have shown how proteins involved in controlling genes work together to carry out their functions in ...

Wealth of genomic hotspots discovered in embryonic stem cells

Jun 13, 2008

In a paper published in Cell on June 13, 2008, Singapore scientists at the Genome Institute of Singapore (GIS) and the National University of Singapore (NUS) unveil an atlas that showing the location of "genomic hotspots" of ess ...

Molecular alliance that sustains embryonic stem cell state

Mar 04, 2008

One of the four ingredients in the genetic recipe that scientists in Japan and the U.S. followed last year to persuade human skin cells to revert to an embryonic stem cell state, is dispensable in ES cells, thanks to the ...

Putting microRNAs on the stem cell map

Aug 07, 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 ...

Recommended for you

Understanding how cells follow electric fields

17 hours ago

Many living things can respond to electric fields, either moving or using them to detect prey or enemies. Weak electric fields may be important growth and development, and in wound healing: it's known that ...

Protein scaffold

May 27, 2015

Right before a cell starts to divide to give birth to a daughter cell, its biochemical machinery unwinds the chromosomes and copies the millions of protein sequences comprising the cell's DNA, which is packaged ...

User comments : 0

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.