Essential Genes Behind Skin Development Identified

Researchers have identified the potential link of p63 gene and Satb1 gene in skin development. 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.)

Vladimir Botchkarev, Professor of Cutaneous Biology and Associate Director of the Centre for Skin Sciences at the University of Bradford, suspected that the key to p63's role lay with chromatin remodeling factors such as Satb1. The skin of mice bred with no p63 gene is slow to develop and markedly thinner than that of normal mice. From these "knockout" mice, Botchkarev was able to learn which other genes were under-expressed and which were over-expressed when p63 was lacking.

Source-Eurekalert