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J Cell Biol. 2010 February 22; 188(4): 446.
PMCID: PMC2828912
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Unpacking condensins' function in ES cells

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The nuclei of ES cells lacking Smc2 (right) are large and misshapen.

Fazzio and Panning reveal that chromatin regulatory proteins common to all eukaryotic cells can have additional, unique functions in embryonic stem (ES) cells.

The study follows on from an RNAi screen in which the authors identified 62 chromatin structural and regulatory factors that were essential for ES cell survival. Two of these proteins were Smc2 and Smc4, which together form the catalytic heart of the condensin complexes that promote chromosome condensation in mitosis and meiosis. Because somatic cells lacking condensins continue to proliferate with relatively minor mitotic defects, Fazzio and Panning wondered why ES cells died in the absence of Smc2 or Smc4.

ES cells lacking the condensin subunits accrued massive amounts of DNA damage and apoptosed in a p53-dependent manner. It isn't clear why ES cells are so sensitive to the loss of condensins, but it may be connected to two other phenotypes seen in ES, but not somatic, cells. After Smc2 or Smc4 knockdown, mitotic ES cells arrested in metaphase and interphase ES cell nuclei were enlarged and misshapen.

This suggests that condensins promote mitotic progression and maintain interphase chromatin compaction in ES cells—functions that they don't have in somatic cells. In fact, 47 of the 62 genes identified in the original screen can be depleted in differentiated cells without affecting viability, indicating that the chromatin of ES cells is fundamentally different from somatic cell chromatin. Author Barbara Panning says that, if cancer progenitor cells are similarly reliant on particular chromatin regulators, it may be possible to target them therapeutically without harming their healthy, differentiated neighbors.

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Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press