Stem cell regulators

Miodrag Stojkovic / Photo Researchers, Inc

The paper:

L. Boyer et al., "Core transcriptional regulatory circuitry in human embryonic stem cells," Cell , 122:947-56, 2005. (Cited in 173 papers) [PUBMED]

The finding:

To characterize transcriptional regulation in human embryonic stem cells Richard Young at the Whitehead Institute and colleagues used a genome-wide analysis with chromatin immunoprecipitation and DNA microarrays, finding that transcription factors OCT4, SOX2, and NANOG target 353 genes, roughly half of which are not expressed. They also found that the three transcription factors co-occupy genes' promoter regions to regulate each others' activity.

The significance:

The study suggests these transcription factors repress genes involved in cell differentiation, which means they might play a role in maintaining embryonic stem cell self-renewal, says Tony Lee, also at the Whitehead and one of the paper's authors. It also suggests that unexpressed genes are repressed but poised for activation during development, says Angie Rizzino, at the University of Nebraska Medical Center, explaining how pluripotency is maintained.

The follow up:

In the group's next paper in 2006, the investigators found that many of the 353 genes are associated with the polycomb complex, a multi-protein complex required to maintain the transcriptionally repressive state of genes.

The questions:

"Are the transcription factors recruiting the polycomb complex, or are they themselves recruited to maintain inactivation?" asks Rizzino. Also, NANOG's role in the whole process is still unclear, he adds - is it controlling for suppression or expression of the 353 genes?