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How key genes cooperate to make healthy skin
Date:9/20/2011

Skin is the body's armor, protecting us from disease agents, injury, excessive water loss, and cold and heat. Yet mutations in a single gene, the gene for the protein p63, cause numerous diseases and malformations of the uppermost layer of skin the epidermis and other tissues. In the epidermis, these range from skin cancers to dysplasias that cause cracking, bleeding, infection, and discoloration.

A research team from the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and spearheaded by colleagues from the University of Bradford in the United Kingdom, including members from Boston University, has learned that p63 acts by directly regulating another protein, Satb1, which is a "genome organizer" it controls gene expression in progenitor cells by temporarily remodeling chromatin, the structure that makes up the chromosomes and contains tightly wound DNA.

The p63 protein is the "master regulator" of epidermal development as a mammalian embryo grows, working with other proteins to closely coordinate the expression and timing of groups of genes that control cell growth and differentiation. Just how p63 performs its complex role has been a mystery, however.

A significant part of the answer lies with Satb1. Discovered a decade ago by a team led by Terumi Kohwi-Shigematsu of Berkeley Lab's Life Sciences Division, Satb1 acts as a molecular machine to regulate gene expression by binding to chromosomal DNA at specific sites, rearranging it to bring essential genes into proximity, and recruiting the additional proteins needed to transcribe those genes. Satb1 has been shown to be crucial in the development of the immune system's T-cells, in T-cell function, and in breast cancer metastasis. Yet the mechanisms that control the expression of the Satb1 gene in different cell types have been as much a mystery as how p63 regulates skin development. (Gene names, as distinct from protein names, are italicized
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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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