A molecular sibling of the cancer-fighting protein p53 orchestrates development of the epidermis by stimulating expression of a chromatin-reorganizing protein, Fessing et al. reveal.

Although it doesn't receive the same attention as its more famous sibling, p63 performs an equally important job. Mice lacking the protein die shortly after birth from dehydration because the epidermis doesn't form properly. Researchers have discovered that p63 acts as a master regulator of epidermal differentiation, but whether it regulates a large number of genes directly or through intermediaries remains unclear.

Fessing et al. found that p63 has an assistant, Satb1, a protein that helps to control chromatin remodeling for the TH2 cytokine and β-globin gene loci. Mice lacking Satb1 show an abnormally thin epidermis and reduced activity of genes that control differentiation of keratinocytes, the most abundant type of epidermal cells.

The researchers discovered that Satb1 adjusts gene activity in part by helping to arrange the epidermal differentiation complex (EDC), a cluster of more than 40 genes that manage skin development. The researchers speculate that Satb1 condenses the EDC, much as it does the TH2 cytokine locus during T cell activation, giving the transcription machinery easy access to the genes. A question to investigate, the researchers say, is whether p63 also acts through Satb1 during differentiation of other cells, such as adult stem cells in the skin.

References

References
Fessing
M.Y.
et al
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2011
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J. Cell Biol.
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