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Molecular alliance that sustains embryonic stem cell state
Date:3/4/2008

2 and Klf5 took over Klf4's role. To understand the molecular basis of the Klf4 redundancy, the scientists studied the DNA binding and transcription activation properties of the three Klfs and found that the profiles of the three Klfs were strikingly similar.

"Most important, the data showed that the other Klfs were bound to the target sites when one of them was depleted." said Dr. Ng. "These Krppel-like factors form a very powerful alliance that work together on regulating common targets. The impact of losing one of them is masked by the other two sibling molecules."

For example, Klfs were found to regulate the Nanog gene and other key genes that must be active for ES cells to be pluripotent, or capable of differentiating into virtually any type of cells. Nanog gene is one of the key pluripotency genes in ES cells.

"We suggest that Nanog and other genes are key effectors for the biological functions of the Klfs in ES cells," Dr. Ng said.

"Together, our study provides new insight into how the core Klf circuitry integrates into the Nanog transcriptional network to specify gene expression unique to ES cells.

The way these factors network with key genes in ES cells suggest a way of how Klf4 (along with the other three reprogramming factors) can jump-start the ES cell gene expression engine in adult cells," he noted.

Although these three Klfs are involved in diverse biological roles, their redundant roles have not been previously appreciated.

"Dr. Ng and his colleagues at the Genome Institute of Singapore again have unraveled another intricacy of what makes a stem cell," said Edison Liu, M.D., Executive Director of GIS. "This work brings us closer to a detailed understanding of the genetic components of stemness."

Alan Colman, Ph.D., internationally recognized leader in stem cell research, said, "Klf4 is a transcription factor that came to prominence recently because it was one of four factors u
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Contact: Cathy Yarbrough
sciencematter@yahoo.com
858-243-1814
Agency for Science, Technology and Research (A*STAR), Singapore
Source:Eurekalert

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